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Zhou Y, Peng J, Xu P, Wang F, Xi J, Zhang H, Hu S, Yan H, Tan L, Cai H, Zhang B, Lan G. Population pharmacokinetics and dosing optimization of teicoplanin in renal transplant patients. Antimicrob Agents Chemother 2025:e0156824. [PMID: 40265953 DOI: 10.1128/aac.01568-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Accepted: 03/26/2025] [Indexed: 04/24/2025] Open
Abstract
The objectives of this study were to investigate the population pharmacokinetic (PK) characteristics of teicoplanin in renal transplant patients and to provide recommendations for optimal teicoplanin dosing regimens. A total of 99 renal transplant patients with 386 plasma samples were enrolled (306 in development and 80 in validation). A population PK analysis and simulations were performed to identify the optimal teicoplanin doses needed to provide an 80% probability of target attainment at 72 h and 168 h using both a trough concentration target of >15 µg/mL and the ratio of 24 h area under the concentration-time curve to the minimum inhibitory concentration >610.4. Teicoplanin was well described by a two-compartment PK model. The final model parameter estimates for clearance, central compartment volume of distribution, intercompartmental clearance, and peripheral compartment volume were 0.711 L/h, 11.3 L, 4.22 L/h, and 35.2 L, respectively. Creatinine clearance (CrCL) was the only covariate that significantly affected teicoplanin clearance. Dosing simulation results showed that standard dosing regimens were unable to meet the treatment needs of all patients, and CrCL-based individual dosing regimens are recommended for both loading dose and maintaining dose. Higher-than-standard teicoplanin doses are necessary to achieve prompt and appropriate drug exposure in renal transplant patients.
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Affiliation(s)
- Yangang Zhou
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Institute of Clinical Pharmacy, Central South University, Changsha, Hunan, China
| | - Jiawei Peng
- Department of Kidney Transplantation, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Ping Xu
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Institute of Clinical Pharmacy, Central South University, Changsha, Hunan, China
| | - Feng Wang
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Institute of Clinical Pharmacy, Central South University, Changsha, Hunan, China
| | - Jun Xi
- Hunan Demeter Instruments Co., Ltd., Changsha, Hunan, China
| | - Hedong Zhang
- Department of Kidney Transplantation, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Shanbiao Hu
- Department of Kidney Transplantation, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Han Yan
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Institute of Clinical Pharmacy, Central South University, Changsha, Hunan, China
| | - Liang Tan
- Department of Kidney Transplantation, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Clinical Research Center for Organ Transplantation in Hunan Province, Changsha, Hunan, China
| | - Hualin Cai
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Institute of Clinical Pharmacy, Central South University, Changsha, Hunan, China
| | - Bikui Zhang
- Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Institute of Clinical Pharmacy, Central South University, Changsha, Hunan, China
| | - Gongbin Lan
- Department of Kidney Transplantation, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
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Mouton JWA, De Clercq A, De Paepe P, Petrovic M, Desmet T, Brüggemann RJ, Schouten JA, Jager NGL, De Cock PA. Pharmacokinetics and Target Attainment of Teicoplanin: A Systematic Review. Clin Pharmacokinet 2025; 64:467-509. [PMID: 40064832 DOI: 10.1007/s40262-025-01483-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/27/2025] [Indexed: 04/30/2025]
Abstract
BACKGROUND AND OBJECTIVE Teicoplanin is a glycopeptide antibiotic used to treat severe Gram-positive infections. This systematic review provides a comprehensive overview of the current knowledge on the pharmacokinetics of teicoplanin across the entire population, with the aim to identify gaps in the existing literature, prioritise pharmacokinetic research, and support optimal dosing strategies. METHODS A systematic literature search of the MEDLINE, Embase, Web of Science, and Scopus databases was conducted. Articles published until 1 October 2024 were identified as eligible when they included a pharmacokinetic analysis of teicoplanin. Relevant pharmacokinetic data were extracted from all included articles. Allometric scaling was carried out for reported values of clearance (CL) and volume of distribution (Vd) to an individual of 70 kg. Articles were categorised into eight subgroups. A qualitative assessment of the included studies was conducted using the clinical pharmacokinetic statement checklist. RESULTS In total, 85 articles were included in this review. Pharmacokinetic data for 186 healthy volunteers, 130 neonates, 788 children, 1434 adult patients, 48 older adults (≥ 65 years), 674 critically ill patients, 33 patients with impaired renal function, and 159 patients with extracorporeal elimination techniques were extracted for a total of 3452 subjects. Unbound concentrations were assessed in 7.1% of the articles. The Vdscaled ranged from 1.5 to 583 L/70 kg. The CLscaled ranged from 0.0073 to 6.38 L/h/70 kg. Covariates on drug disposition were identified in 55.3% of studies, 65.6% of which identified a relationship between renal function and CL. Target attainment was described in 42.4% of articles. Dosing recommendations were provided in 61.2% of all studies. Studies had an average quality score of 69.9% ± standard deviation 15.7. CONCLUSION Individual dosing strategies based on renal function need to be developed, particularly in patients with immature or impaired renal function, using state-of-the art pharmacokinetic/pharmacodynamic modelling approaches. Since teicoplanin is highly plasma protein bound and it is suggested that total concentrations cannot be easily translated to unbound concentrations, future research should also include the measurement of unbound concentrations for pharmacokinetic and target attainment evaluation. TRIAL REGISTRATION Prospectively registered in PROSPERO. TRIAL REGISTRATION NUMBER CRD42023483334. Registration date: 03/12/2023.
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Affiliation(s)
- Jaap W A Mouton
- Department of Pharmacy, Pharmacology and Toxicology, Radboud University Medical Center, Research Institute for Medical Innovation, Nijmegen, The Netherlands
| | - Arnaud De Clercq
- Department of Basic and Applied Medical Sciences, Ghent University, Ghent, Belgium
- Department of Emergency Medicine, Ghent University Hospital, Ghent, Belgium
| | - Peter De Paepe
- Department of Basic and Applied Medical Sciences, Ghent University, Ghent, Belgium
- Department of Emergency Medicine, Ghent University Hospital, Ghent, Belgium
| | - Mirko Petrovic
- Section of Geriatrics, Department of Internal Medicine and Paediatrics, Ghent University, Ghent, Belgium
| | - Tania Desmet
- Department of Emergency Medicine, Ghent University Hospital, Ghent, Belgium
| | - Roger J Brüggemann
- Department of Pharmacy, Pharmacology and Toxicology, Radboud University Medical Center, Research Institute for Medical Innovation, Nijmegen, The Netherlands
| | - Jeroen A Schouten
- Department of Intensive Care, Radboud University Medical Center, Research Institute for Medical Innovation, Nijmegen, The Netherlands
| | - Nynke G L Jager
- Department of Pharmacy, Pharmacology and Toxicology, Radboud University Medical Center, Research Institute for Medical Innovation, Nijmegen, The Netherlands
| | - Pieter A De Cock
- Department of Basic and Applied Medical Sciences, Ghent University, Ghent, Belgium.
- Department of Pharmacy, Ghent University Hospital, Ghent, Belgium.
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Kondo S, Oda K, Kaneko T, Jono H, Saito H. Teicoplanin 24-h loading dose regimen using a decision tree model to target serum trough concentration of 15-30 μg/mL: A retrospective study. J Infect Chemother 2025; 31:102564. [PMID: 39571973 DOI: 10.1016/j.jiac.2024.11.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 11/11/2024] [Accepted: 11/18/2024] [Indexed: 11/25/2024]
Abstract
INTRODUCTION Teicoplanin (TEIC) is typically administered as a loading dose over 36-48 h. Achieving an effective concentration quickly is expected to treat severe infections, such as sepsis and methicillin-resistant Staphylococcus aureus infections. We aimed to identify the TEIC loading dose to be completed within 24 h, targeting the concentration of 15-30 μg/mL and factors affecting the loading dose by utilizing the decision tree (DT) model. METHODS Patients treated with TEIC between January 2017 and December 2022 who met the 24-h loading dose regimen were enrolled. A LD22.5 (corrected TEIC loading dose targeting concentration of 22.5 μg/mL) was determined, factors affecting the concentration were extracted, and a DT model was constructed. The validity of the DT was assessed using the coefficient of determination (R2) in the DT and population pharmacokinetics (PopPK) models for LD22.5. RESULT A total of 149 patients were divided into training (n = 104, 70 %) and test groups (n = 45, 30 %). We indicated an average of 14.5 mg/kg for LD22.5 and extracted four factors (estimated glomerular filtration rate, age, albumin, and C-reactive protein) from the DT model. The R2 values were 0.724, 0.695, 0.681, and 0.653 for the DT models (training and test groups) and two PopPK models, respectively. CONCLUSION We established a 24-h loading dose regimen targeting the TEIC concentration of 15-30 μg/mL and identified four factors affecting the loading dose by using DT. By following the indicated DT algorithm flowchat, optimal decisions regarding the loading dose could be made for TEIC therapy.
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Affiliation(s)
- Shoji Kondo
- Department of Pharmacy, Kumamoto University Hospital, 1-1-1, Honjo, Chuo-ku, Kumamoto, Japan; Department of Infection Control, Kumamoto University Hospital, 1-1-1, Honjo, Chuo-ku, Kumamoto, Japan; Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences Kumamoto University, 5-1, Oe, Chuo-ku, Kumamoto, Japan.
| | - Kazutaka Oda
- Department of Pharmacy, Kumamoto University Hospital, 1-1-1, Honjo, Chuo-ku, Kumamoto, Japan; Department of Infection Control, Kumamoto University Hospital, 1-1-1, Honjo, Chuo-ku, Kumamoto, Japan.
| | - Tetsuya Kaneko
- Department of Pharmacy, Kumamoto University Hospital, 1-1-1, Honjo, Chuo-ku, Kumamoto, Japan.
| | - Hirofumi Jono
- Department of Pharmacy, Kumamoto University Hospital, 1-1-1, Honjo, Chuo-ku, Kumamoto, Japan; Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences Kumamoto University, 5-1, Oe, Chuo-ku, Kumamoto, Japan.
| | - Hideyuki Saito
- Department of Pharmacy, Kumamoto University Hospital, 1-1-1, Honjo, Chuo-ku, Kumamoto, Japan; Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences Kumamoto University, 5-1, Oe, Chuo-ku, Kumamoto, Japan.
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Liu T, Wu J, Na P, Wu X, Yuan Y, Wang C, Ma X, Qi L, Chen X, Rao W, Duan Z, Fang X, Xie L, Li H. Necessity for higher teicoplanin doses in older adults: a multicenter prospective observational study in China. BMC Geriatr 2024; 24:487. [PMID: 38831261 PMCID: PMC11149339 DOI: 10.1186/s12877-024-05091-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Accepted: 05/17/2024] [Indexed: 06/05/2024] Open
Abstract
BACKGROUND Many older adult patients receive low-dose teicoplanin with varied regimens, leading to a lack of clarity on its optimal regimens and toxicity profiles in China. This study aimed to clarify these aspects by analyzing teicoplanin treatment concentrations and toxicities. METHODS We included older adult patients administered teicoplanin at four tertiary hospitals in Beijing from June 2021 to July 2023, targeting a trough concentration (Cmin) ≥ 10 mg/L. Teicoplanin concentrations and toxicities were monitored dynamically. RESULTS From 204 patients, we obtained 632 teicoplanin concentrations. Most patients (83.3%) received low-dose regimens. Suboptimal concentrations were found in 66.4% of patients within 7 days of treatment and 17.0% after 15 days. Cmin gradually increased with treatment duration and was influenced initially by creatinine and by both body weight and creatinine from days 8 to 14. The target concentration was achieved in 53.1%, 33.9%, 15.6%, and 5.5% of patients at 3, ≤ 7, 8-14, and ≥ 15 days after withdrawal, respectively. Slow elimination was associated with average Cmin and eGFR. Nephrotoxicity, hepatotoxicity, and thrombocytopenia occurred in 12.5%, 4.1%, and 31.5% of patients, respectively, without significant differences between concentrations. CONCLUSIONS Most older adult patients were underdosed, indicating a need for dose adjustment. Given the varied risk factors for suboptimal concentrations in different treatment stages, a one-size-fits-all regimen was ineffective. We recommend an initial dose of 400 mg at 12-h intervals for the first three days, with subsequent doses from days 4 to 14 adjusted based on creatinine and body weight; after day 14, a maintenance dose of 200 mg daily is advised. TRIAL REGISTRATION ChiCTR2100046811; 28/05/2021.
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Affiliation(s)
- Tingting Liu
- Department of Pulmonary and Critical Care Medicine, The Second Medical Center, National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, 100853, China
- Chinese PLA Medical School, Beijing, 100853, China
| | - Jionghe Wu
- Department of Pulmonary and Critical Care Medicine, The Second Medical Center, National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, 100853, China
| | - Peng Na
- Chinese PLA Medical School, Beijing, 100853, China
| | - Xia Wu
- Chinese PLA Medical School, Beijing, 100853, China
| | - Yaping Yuan
- Department of Pulmonary and Critical Care Medicine, The Second Medical Center, National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, 100853, China
| | - Chao Wang
- Department of Pulmonary and Critical Care Medicine, The Fourth Medical Center, Chinese PLA General Hospital, Beijing, 100853, China
| | - Xuewei Ma
- Department of Pulmonary and Critical Care Medicine, The Second Medical Center, National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, 100853, China
| | - Lin Qi
- Department of Pulmonary and Critical Care Medicine, The Second Medical Center, National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, 100853, China
| | | | - Weiqiao Rao
- BGI Genomics Co., Ltd, Shenzhen, 518083, China
| | - Zhimei Duan
- Department of Pulmonary and Critical Care Medicine, The First Medical Center, Chinese PLA General Hospital, Beijing, 100853, China
| | - Xiangqun Fang
- Department of Pulmonary and Critical Care Medicine, The Second Medical Center, National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, 100853, China.
| | - Lixin Xie
- College of Pulmonary & Critical Care Medicine, Chinese PLA General Hospital, Beijing, 100853, China.
| | - Hongxia Li
- Department of Pulmonary and Critical Care Medicine, The Second Medical Center, National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, 100853, China.
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Saito N, Tsuchiya J, Itoga M, Okamura Y, Tsuyama H, Kimura M, Inoue F, Kimura T, Ozaki H, Tono Y, Minakawa S, Tomita H. Multiple Blood Culture Sampling, Proper Antimicrobial Choice, and Adequate Dose in Definitive Therapy Supported by the Antimicrobial Stewardship Team Could Decrease 30-Day Sepsis Mortality Rates. Infect Drug Resist 2024; 17:207-219. [PMID: 38283110 PMCID: PMC10812706 DOI: 10.2147/idr.s445917] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Accepted: 01/11/2024] [Indexed: 01/30/2024] Open
Abstract
Objective This study aimed to identify factors that should be focused on by the antimicrobial stewardship team for treating patients with sepsis, by investigating the mortality of patients with sepsis within 30 days and the mortality-related factors in our hospital over a 10-year period from the perspective of appropriate antimicrobial use. Methods Factors associated with 30-day mortality were investigated using hierarchical multiple logistic regression in 1406 patients with pathogen-identified sepsis in Hirosaki University Hospital. These factors were clinical data, microbiological data, antimicrobials used in empiric and definitive therapies, presence/absence of ineffective use, underdosing as evaluated using Monte Carlo simulation, and practice of de-escalation. Results The ineffective use of antimicrobials in empiric therapy and the underdosing and ineffective use in definitive therapy were significantly associated with 30-day mortality (odds ratio [OR] = 2.70, 3.72, and 3.65, respectively). Multiple blood culture sampling was inversely associated with these inappropriate antimicrobial uses. Every year, the 30-day mortality rate has been decreasing, in line with the increase in multiple blood culture sampling and de-escalation; the inappropriate use of antimicrobials has also decreased. Conclusion Multiple blood culture sampling, proper choice of antimicrobial, and using an adequate dose in definitive therapy could decrease the 30-day mortality rate in patients with sepsis and these factors could be supported by the antimicrobial stewardship team.
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Affiliation(s)
- Norihiro Saito
- Division of Infection Control and Prevention, Hirosaki University Hospital, Hirosaki, Aomori, Japan
- Department of Clinical Laboratory Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
- Division of Clinical Laboratory, Hirosaki University Hospital, Hirosaki, Aomori, Japan
| | - Junichiro Tsuchiya
- Division of Infection Control and Prevention, Hirosaki University Hospital, Hirosaki, Aomori, Japan
- Division of Clinical Laboratory, Hirosaki University Hospital, Hirosaki, Aomori, Japan
| | - Masamichi Itoga
- Division of Infection Control and Prevention, Hirosaki University Hospital, Hirosaki, Aomori, Japan
- Department of Clinical Laboratory Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
| | - Yuji Okamura
- Division of Infection Control and Prevention, Hirosaki University Hospital, Hirosaki, Aomori, Japan
- Division of Pharmacy, Hirosaki University Hospital, Hirosaki, Aomori, Japan
| | - Hiromasa Tsuyama
- Division of Infection Control and Prevention, Hirosaki University Hospital, Hirosaki, Aomori, Japan
- Division of Pharmacy, Hirosaki University Hospital, Hirosaki, Aomori, Japan
| | - Masahiko Kimura
- Division of Infection Control and Prevention, Hirosaki University Hospital, Hirosaki, Aomori, Japan
- Division of Clinical Laboratory, Hirosaki University Hospital, Hirosaki, Aomori, Japan
| | - Fumio Inoue
- Division of Infection Control and Prevention, Hirosaki University Hospital, Hirosaki, Aomori, Japan
- Division of Clinical Laboratory, Hirosaki University Hospital, Hirosaki, Aomori, Japan
| | - Toshiyuki Kimura
- Division of Infection Control and Prevention, Hirosaki University Hospital, Hirosaki, Aomori, Japan
| | - Hiromi Ozaki
- Division of Infection Control and Prevention, Hirosaki University Hospital, Hirosaki, Aomori, Japan
| | - Yuka Tono
- Division of Infection Control and Prevention, Hirosaki University Hospital, Hirosaki, Aomori, Japan
- Division of Pharmacy, Hirosaki University Hospital, Hirosaki, Aomori, Japan
| | - Satoko Minakawa
- Division of Infection Control and Prevention, Hirosaki University Hospital, Hirosaki, Aomori, Japan
- Division of Clinical Laboratory, Hirosaki University Hospital, Hirosaki, Aomori, Japan
| | - Hirofumi Tomita
- Department of Clinical Laboratory Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
- Division of Clinical Laboratory, Hirosaki University Hospital, Hirosaki, Aomori, Japan
- Department of Cardiology and Nephrology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan
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Wang Y, Yao F, Chen S, Ouyang X, Lan J, Wu Z, Wang Y, Chen J, Wang X, Chen C. Optimal Teicoplanin Dosage Regimens in Critically Ill Patients: Population Pharmacokinetics and Dosing Simulations Based on Renal Function and Infection Type. Drug Des Devel Ther 2023; 17:2259-2271. [PMID: 37546521 PMCID: PMC10404122 DOI: 10.2147/dddt.s413662] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2023] [Accepted: 07/05/2023] [Indexed: 08/08/2023] Open
Abstract
Purpose To develop a population pharmacokinetic model describing teicoplanin concentrations in patients hospitalized in intensive care unit (ICU) and to perform Monte Carlo simulations to provide detailed dosing regimens of teicoplanin. Methods This single-center, prospective, observational study was conducted on 151 patients in ICU with 347 plasma samples. The population pharmacokinetics model was established and various covariates were evaluated. The probability of target attainment (PTA) of various proposal dosing regimens was calculated by Monte Carlo simulations. Results The two-compartment model adequately described teicoplanin concentration-time data. The estimated glomerular filtration rate (eGFR) associated with systemic clearance (CL) was the only covariate included in the final model. The estimate of CL was 0.838 L/h, with the eGFR adjustment factor of 0.00823. The volume of the central compartment (Vc), inter-compartmental clearance (Q) and volumes of the peripheral compartments (Vp) were 14.4 L, 3.08 L/h and 51.6 L, respectively. The simulations revealed that the standard dosage regimen was only sufficient for the patients with severe renal dysfunction (eGFR ≤ 30 mL/min/1.73 m2) to attain target trough concentration (Cmin, PTA 52.8%). When eGFR > 30 mL/min/1.73 m2, increasing dose and the administration times of loading doses were the preferred options to achieve target Cmin based on the renal function and types of infection. Conclusion The most commonly used standard dosage regimen was insufficient for all ICU patients. Our study provided detailed dosing regimens of teicoplanin stratified by eGFR and types of infection for ICU patients.
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Affiliation(s)
- Yifan Wang
- Department of Critical Care Medicine, Shenzhen People’s Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518020, People’s Republic of China
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou, 510006, People’s Republic of China
| | - Fen Yao
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou, 510006, People’s Republic of China
| | - Shenglong Chen
- Department of Critical Care Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China
| | - Xin Ouyang
- Department of Intensive Care Unit of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China
| | - Jinhua Lan
- Department of Pharmacy, General Hospital of Southern Theatre Command, Guangzhou, 510010, People’s Republic of China
| | - Zheng Wu
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou, 510006, People’s Republic of China
| | - Yirong Wang
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou, 510006, People’s Republic of China
| | - Jingchun Chen
- School of Biology and Biological Engineering, South China University of Technology, Guangzhou, 510006, People’s Republic of China
| | - Xipei Wang
- Research Center of Medical Sciences, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China
- Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China
| | - Chunbo Chen
- Department of Critical Care Medicine, Shenzhen People’s Hospital, The Second Clinical Medical College of Jinan University, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518020, People’s Republic of China
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Oda K, Saito H, Jono H. Bayesian prediction-based individualized dosing of anti-methicillin-resistant Staphylococcus aureus treatment: Recent advancements and prospects in therapeutic drug monitoring. Pharmacol Ther 2023; 246:108433. [PMID: 37149156 DOI: 10.1016/j.pharmthera.2023.108433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 04/19/2023] [Accepted: 05/02/2023] [Indexed: 05/08/2023]
Abstract
As one of the efficient techniques for TDM, the population pharmacokinetic (popPK) model approach for dose individualization has been developed due to the rapidly growing innovative progress in computer technology and has recently been considered as a part of model-informed precision dosing (MIPD). Initial dose individualization and measurement followed by maximum a posteriori (MAP)-Bayesian prediction using a popPK model are the most classical and widely used approach among a class of MIPD strategies. MAP-Bayesian prediction offers the possibility of dose optimization based on measurement even before reaching a pharmacokinetically steady state, such as in an emergency, especially for infectious diseases requiring urgent antimicrobial treatment. As the pharmacokinetic processes in critically ill patients are affected and highly variable due to pathophysiological disturbances, the advantages offered by the popPK model approach make it highly recommended and required for effective and appropriate antimicrobial treatment. In this review, we focus on novel insights and beneficial aspects of the popPK model approach, especially in the treatment of infectious diseases with anti-methicillin-resistant Staphylococcus aureus agents represented by vancomycin, and discuss the recent advancements and prospects in TDM practice.
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Affiliation(s)
- Kazutaka Oda
- Department of Pharmacy, Kumamoto University Hospital, 1-1-1 Honjo, Chuo-ku, Kumamoto, Japan
| | - Hideyuki Saito
- Department of Pharmacy, Kumamoto University Hospital, 1-1-1 Honjo, Chuo-ku, Kumamoto, Japan; Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University; 1-1-1, Honjo, Chuo-ku, Kumamoto, Japan
| | - Hirofumi Jono
- Department of Pharmacy, Kumamoto University Hospital, 1-1-1 Honjo, Chuo-ku, Kumamoto, Japan; Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University; 1-1-1, Honjo, Chuo-ku, Kumamoto, Japan.
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Therapeutic Drug Monitoring and Population Pharmacokinetic Analysis of Teicoplanin among Chinese Patients with Gram-Positive Infections in a Tertiary Hospital. J Clin Pharm Ther 2023. [DOI: 10.1155/2023/2681979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/18/2023]
Abstract
Background. To explore the use of teicoplanin among Chinese patients with Gram-positive infections in a tertiary hospital. Methods. The medical records of patients, who were monitored for teicoplanin plasma concentration (TPC) from December 2017 to February 2019, were collected. By combining the therapeutic drug monitoring (TDM) and nonlinear mixed-effects model, a population pharmacokinetic (PPK) model of teicoplanin was established. Results. The proportions of TPCs lower and higher than 10 mg/L were nearly the same (102 vs. 108 cases). A two-compartment model of teicoplanin PPK in Chinese patients was established. Compared with 400 mg, the 600 mg regimen was more able to reach the target concentration (10 mg/L), especially for high-weight patients. Conclusions. The standard regimen of teicoplanin, 400 mg, failed to reach the target value in the present population. Moreover, the 600 mg regimen was feasible for high-weight patients based on TDM and individualized pharmacokinetic dosing adjustment.
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Ma P, Liu R, Gu W, Dai Q, Gan Y, Cen J, Shang S, Liu F, Chen Y. Construction and Interpretation of Prediction Model of Teicoplanin Trough Concentration via Machine Learning. Front Med (Lausanne) 2022; 9:808969. [PMID: 35360734 PMCID: PMC8963816 DOI: 10.3389/fmed.2022.808969] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 01/25/2022] [Indexed: 02/02/2023] Open
Abstract
Objective To establish an optimal model to predict the teicoplanin trough concentrations by machine learning, and explain the feature importance in the prediction model using the SHapley Additive exPlanation (SHAP) method. Methods A retrospective study was performed on 279 therapeutic drug monitoring (TDM) measurements obtained from 192 patients who were treated with teicoplanin intravenously at the First Affiliated Hospital of Army Medical University from November 2017 to July 2021. This study included 27 variables, and the teicoplanin trough concentrations were considered as the target variable. The whole dataset was divided into a training group and testing group at the ratio of 8:2, and predictive performance was compared among six different algorithms. Algorithms with higher model performance (top 3) were selected to establish the ensemble prediction model and SHAP was employed to interpret the model. Results Three algorithms (SVR, GBRT, and RF) with high R2 scores (0.676, 0.670, and 0.656, respectively) were selected to construct the ensemble model at the ratio of 6:3:1. The model with R2 = 0.720, MAE = 3.628, MSE = 22.571, absolute accuracy of 83.93%, and relative accuracy of 60.71% was obtained, which performed better in model fitting and had better prediction accuracy than any single algorithm. The feature importance and direction of each variable were visually demonstrated by SHAP values, in which teicoplanin administration and renal function were the most important factors. Conclusion We firstly adopted a machine learning approach to predict the teicoplanin trough concentration, and interpreted the prediction model by the SHAP method, which is of great significance and value for the clinical medication guidance.
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Affiliation(s)
- Pan Ma
- Department of Pharmacy, The First Affiliated Hospital of Third Military Medical University (Army Medical University), Chongqing, China
| | - Ruixiang Liu
- Department of Pharmacy, The First Affiliated Hospital of Third Military Medical University (Army Medical University), Chongqing, China
| | - Wenrui Gu
- Department of Pharmacy, The First Affiliated Hospital of Third Military Medical University (Army Medical University), Chongqing, China
| | - Qing Dai
- Department of Pharmacy, The First Affiliated Hospital of Third Military Medical University (Army Medical University), Chongqing, China
| | - Yu Gan
- Department of Pharmacy, The First Affiliated Hospital of Third Military Medical University (Army Medical University), Chongqing, China
| | - Jing Cen
- Department of Pharmacy, The First Affiliated Hospital of Third Military Medical University (Army Medical University), Chongqing, China
| | - Shenglan Shang
- Department of Clinical Pharmacy, General Hospital of Central Theater Command of PLA, Wuhan, China
| | - Fang Liu
- Department of Pharmacy, The First Affiliated Hospital of Third Military Medical University (Army Medical University), Chongqing, China
| | - Yongchuan Chen
- Department of Pharmacy, The First Affiliated Hospital of Third Military Medical University (Army Medical University), Chongqing, China
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10
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Bian X, Qu X, Zhang J, Nang SC, Bergen PJ, Tony Zhou Q, Chan HK, Feng M, Li J. Pharmacokinetics and pharmacodynamics of peptide antibiotics. Adv Drug Deliv Rev 2022; 183:114171. [PMID: 35189264 PMCID: PMC10019944 DOI: 10.1016/j.addr.2022.114171] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 01/23/2022] [Accepted: 02/16/2022] [Indexed: 01/05/2023]
Abstract
Antimicrobial resistance is a major global health challenge. As few new efficacious antibiotics will become available in the near future, peptide antibiotics continue to be major therapeutic options for treating infections caused by multidrug-resistant pathogens. Rational use of antibiotics requires optimisation of the pharmacokinetics and pharmacodynamics for the treatment of different types of infections. Toxicodynamics must also be considered to improve the safety of antibiotic use and, where appropriate, to guide therapeutic drug monitoring. This review focuses on the pharmacokinetics/pharmacodynamics/toxicodynamics of peptide antibiotics against multidrug-resistant Gram-negative and Gram-positive pathogens. Optimising antibiotic exposure at the infection site is essential for improving their efficacy and minimising emergence of resistance.
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Affiliation(s)
- Xingchen Bian
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Clinical Pharmacology of Antibiotics, Shanghai, China; National Health Commission & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China; School of Pharmacy, Fudan University, Shanghai, China
| | - Xingyi Qu
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Clinical Pharmacology of Antibiotics, Shanghai, China; National Health Commission & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China; School of Pharmacy, Fudan University, Shanghai, China; Phase I Unit, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Jing Zhang
- Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Clinical Pharmacology of Antibiotics, Shanghai, China; National Health Commission & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China; Phase I Unit, Huashan Hospital, Fudan University, Shanghai 200040, China
| | - Sue C Nang
- Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Australia
| | - Phillip J Bergen
- Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Australia
| | - Qi Tony Zhou
- Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, IN, USA
| | - Hak-Kim Chan
- Advanced Drug Delivery Group, School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Meiqing Feng
- School of Pharmacy, Fudan University, Shanghai, China
| | - Jian Li
- Biomedicine Discovery Institute and Department of Microbiology, Monash University, Melbourne, Australia.
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11
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Wu W, Liu M, Geng JJ, Wang M. Teicoplanin combined with conventional vancomycin therapy for the treatment of pulmonary methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis infections. World J Clin Cases 2021; 9:10549-10556. [PMID: 35004986 PMCID: PMC8686121 DOI: 10.12998/wjcc.v9.i34.10549] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 08/24/2021] [Accepted: 10/14/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Vancomycin and teicoplanin are both antibiotics that have significant antimicrobial effects on Gram-positive cocci.
AIM To explore the value of teicoplanin combined with conventional (vancomycin only) anti-infective therapy for the treatment of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis pulmonary infections.
METHODS A total of 86 patients with methicillin-resistant Staphylococcus aureus or methicillin-resistant Staphylococcus epidermidis pulmonary infections, treated in our hospital between January 2018 and February 2020, were assigned to the study and control groups using a random number table method, with 43 patients in each group. The control group received conventional treatment (vancomycin), and the study group received both teicoplanin and conventional treatment. The following indicators were assessed in both groups: the time required for symptom relief, treatment effectiveness, serum levels of inflammatory factors (procalcitonin, interleukin-1β, tumor necrosis factor-α, C-reactive protein), clinical pulmonary infection scores before and after treatment, and the incidence of adverse reactions.
RESULTS Patients in the study group were observed to have faster cough and expectoration resolution, white blood cell count normalization, body temperature normalization, and rales disappearance than patients in the control group (all P < 0.05); the total rate of effectiveness was 93.02% in the study group, higher than the 76.74% in the control group (P < 0.05). The pre-treatment serum levels of procalcitonin, interleukin-1β, tumor necrosis factor-α, and C-reactive protein as well as the clinical pulmonary infection scores were similar among the patients in both groups. However, the post-treatment serum levels of procalcitonin, interleukin-1β, tumor necrosis factor-α, and C-reactive protein as well as the clinical pulmonary infection scores were significantly lower in the study group than in the control group (P < 0.05). There was no significant difference in the incidence of adverse reactions between the groups.
CONCLUSION Compared with conventional (vancomycin only) therapy, teicoplanin and vancomycin combination therapy for patients with pulmonary methicillin-resistant Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis infections can improve patient clinical symptoms, modulate serum inflammatory factor levels, and improve treatment efficacy, without increasing the risk of adverse reactions.
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Affiliation(s)
- Wei Wu
- Laboratory Medicine, Bejing Tongren Hospital, Capital Medical University, Beijing 100176, China
| | - Min Liu
- Department of General Practice, The Community Health Services Center in Lumen, Beijing 100080, China
| | - Jia-Jing Geng
- Laboratory Medicine, Bejing Tongren Hospital, Capital Medical University, Beijing 100176, China
| | - Mei Wang
- Laboratory Medicine, Bejing Tongren Hospital, Capital Medical University, Beijing 100176, China
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12
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Xu J, Lin R, Chen Y, You X, Huang P, Lin C. Physiologically Based Pharmacokinetic Modeling and Dose Adjustment of Teicoplanin in Pediatric Patients With Renal Impairment. J Clin Pharmacol 2021; 62:620-630. [PMID: 34761398 DOI: 10.1002/jcph.2000] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 11/07/2021] [Indexed: 12/29/2022]
Abstract
The pharmacokinetics of teicoplanin differs in children as compared with adults, and especially in renally impaired pediatric patients. Inappropriate empirical antibacterial therapy may lead to treatment-related antibacterial resistance and increased toxicity, making adjustment of the dosage regimen essential. In the present study, physiologically based pharmacokinetic (PBPK) models were developed to define the appropriate dosage regimen for pediatric patients with differing renal function. Our PBPK models accurately predicted teicoplanin exposures in both adult and pediatric subjects after single and multiple intravenous infusions, with a <1.36-fold error between predicted and observed data, and all observed data were within minimal and maximal data of the corresponding population simulation. The area under the plasma concentration-time curve was predicted to increase 1.25-fold, 1.95-fold, and 2.82-fold in pediatric patients with mild, moderate, and severe renal impairment, respectively, relative to that of healthy children. Subsequently, the results of Monte Carlo simulations indicated that the recommended dosing of 12, 9.5, 6, and 4 mg/kg at 12-hour intervals would be appropriate in pediatric patients with normal renal function and in those with mild, moderate, and severe renal impairment, respectively, at a susceptible minimum inhibitory concentration <2 mg/L. In conclusion, our PBPK model with an incorporated Monte Carlo simulation can provide improved guidance on dosing in pediatric patients with differing renal function and provide a basis for precision therapy with teicoplanin.
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Affiliation(s)
- Jianwen Xu
- Department of Pharmacy, the First Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China
| | - Rongfang Lin
- Department of Pharmacy, the First Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China
| | - Yong Chen
- Department of Pharmacy, Fuzhou Children's Hospital of Fujian Medical University, Fuzhou, 350005, People's Republic of China
| | - Xiang You
- Department of Pharmacy, the First Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China
| | - Pinfang Huang
- Department of Pharmacy, the First Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China
| | - Cuihong Lin
- Department of Pharmacy, the First Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China
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13
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Tsuji Y. Hospital Pharmacometrics for Optimal Individual Administration of Antimicrobial Agents for Anti-methicillin-resistant Staphylococcus aureus Infected Patients. Biol Pharm Bull 2021; 44:1174-1183. [PMID: 34471044 DOI: 10.1248/bpb.b21-00002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Therapeutic drug monitoring and target concentration intervention based on population pharmacokinetic and pharmacodynamic models has been strongly recommended for anti-methicillin-resistant Staphylococcus aureus (MRSA) agents in order to provide appropriate antimicrobial chemotherapy to each individual patient, and pharmacokinetic and pharmacodynamic analyses in hospitalized patients have been actively conducted, as evidenced with vancomycin. Teicoplanin, daptomycin, and linezolid have been the most studied antibiotics, using population pharmacokinetics of patients with MRSA. Infections caused by MRSA have higher severity and fatality rates than other antimicrobial-susceptible infections. Therefore, many medical facilities have been implementing infection control programs based on antimicrobial stewardship to prevent nosocomial infections and drug-resistant strains. Studies detailing pharmacometrics for these antibiotics have been reported to elucidate the pharmacokinetic and pharmacodynamic properties, to determine significant factors influencing variabilities between individuals, and to develop target concentration interventions and dosing regimens for adults, the elderly, patients with renal insufficiency including those on continuous renal replacement therapies, patients with low body weight, obese patients, and pediatric patients. This review presents the details of our recent research on the optimal dosing design of antimicrobial agents for the treatment of MRSA infection based on hospital pharmacometrics. In addition, the prospect of using modeling and simulation has shown major advantages in supporting dosing regimen selection.
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Affiliation(s)
- Yasuhiro Tsuji
- Center for Pharmacist Education, School of Pharmacy, Nihon University
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14
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Sako KI, Nakamaru Y, Ikawa K, Maeda T, Goto S, Ishihara Y, Kato Y, Matsuda Y. Population Pharmacokinetics of Teicoplanin and Its Dosing Recommendations for Neutropenic Patients With Augmented Renal Clearance for Hematological Malignancies. Ther Drug Monit 2021; 43:519-526. [PMID: 34250964 DOI: 10.1097/ftd.0000000000000906] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Accepted: 04/30/2021] [Indexed: 11/26/2022]
Abstract
BACKGROUND Plasma teicoplanin concentrations do not reach the therapeutic range in several patients with hematological malignancies. Nevertheless, the characteristics of the population pharmacokinetic (PPK) models have not been clarified for malignancy. The decrease in the teicoplanin concentration in patients with cancer has been attributed to augmented renal clearance (ARC). It is essential to identify the causative factors of ARC to construct a PPK model to optimize the administration method. The authors aimed to establish a PPK model and develop an appropriate dosing regimen for teicoplanin in patients with hematological malignancies. METHODS PPK analysis was performed using therapeutic drug monitoring (TDM) data from 119 patients with hematological malignancies. The developed model was verified by predictive performance. RESULTS The covariates affecting systemic clearance were serum creatinine, presence or absence of neutropenia (<500/μL), and body size descriptor. Patients with hematologic malignancies and neutropenia showed a 25% increase in clearance compared with those with a normal neutrophil count. The PPK model was constructed based on the presence or absence of neutropenia. This model allowed the selection of the most appropriate dosage regimen out of those recommended by the TDM guidelines for patients with eGFR of >60 mL/min/1.73 m2. The PPK model predicted a dosing regimen for achieving a 10% improvement in the coverage probability of the target concentration range during the loading and maintenance phases. CONCLUSIONS The PPK model may help optimize dose regimens and evaluate dosing methods, using comparative simulations, in patients with hematological malignancies.
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Affiliation(s)
- Ken-Ichi Sako
- Department of Clinical Pharmacy, Nihon Pharmaceutical University, Saitama, Japan
- Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan; and
| | - Yuta Nakamaru
- Department of Clinical Pharmacy, Nihon Pharmaceutical University, Saitama, Japan
| | - Kazuro Ikawa
- Department of Clinical Pharmacy, Nihon Pharmaceutical University, Saitama, Japan
| | - Tomoji Maeda
- Department of Clinical Pharmacy, Nihon Pharmaceutical University, Saitama, Japan
| | - Sotaro Goto
- Department of Pharmacy, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
| | - Yoko Ishihara
- Department of Pharmacy, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
| | - Yukio Kato
- Faculty of Pharmacy, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan; and
| | - Yoshikazu Matsuda
- Department of Clinical Pharmacy, Nihon Pharmaceutical University, Saitama, Japan
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15
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Watanabe E, Matsumoto K, Ikawa K, Yokoyama Y, Shigemi A, Enoki Y, Umezaki Y, Nakamura K, Ueno K, Terazono H, Morikawa N, Takeda Y. Pharmacokinetic/pharmacodynamic evaluation of teicoplanin against Staphylococcus aureus in a murine thigh infection model. J Glob Antimicrob Resist 2020; 24:83-87. [PMID: 33290889 DOI: 10.1016/j.jgar.2020.11.014] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Revised: 10/04/2020] [Accepted: 11/11/2020] [Indexed: 11/15/2022] Open
Abstract
OBJECTIVES Pharmacokinetic/pharmacodynamic (PK/PD) analysis using murine infection models is a well-established methodology for optimising antimicrobial therapy. Therefore, we investigated the PK/PD indices of teicoplanin againstStaphylococcus aureus using a murine thigh infection model. METHODS Mice were rendered neutropenic by administration of a two-step dosing of cyclophosphamide. Then, isolates of methicillin-susceptibleS. aureus (MSSA) or methicillin-resistant S. aureus (MRSA) were inoculated into the thighs of neutropenic mice. PK/PD analyses were performed by non-linear least-squared regression using the MULTI program. RESULTS Target values offCmax/MIC (r2 = 0.94) of teicoplanin for static effect and 1 log10 kill against MSSA were 4.44 and 15.44, respectively. Target values of fAUC24/MIC (r2 = 0.92) of teicoplanin for static effect and 1 log10 kill against MSSA were 30.4 and 70.56, respectively. Target values of fCmax/MIC (r2 = 0.91) of teicoplanin for static effect and 1 log10 kill against MRSA were 8.92 and 14.16, respectively. Target values of fAUC24/MIC (r2 = 0.92) of teicoplanin for static effect and 1 log10 kill against MRSA were 54.8 and 76.4, respectively. CONCLUSION These results suggest thatfCmax/MIC and fAUC24/MIC are useful PK/PD indices of teicoplanin against MSSA and MRSA.
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Affiliation(s)
- Erika Watanabe
- Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan
| | - Kazuaki Matsumoto
- Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan
| | - Kazuro Ikawa
- Department of Clinical Pharmacotherapy, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
| | - Yuta Yokoyama
- Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan
| | - Akari Shigemi
- Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan
| | - Yuki Enoki
- Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan
| | - Yasuhiro Umezaki
- Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan
| | - Koyo Nakamura
- Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan
| | - Keiichiro Ueno
- Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan
| | - Hideyuki Terazono
- Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan
| | - Norifumi Morikawa
- Department of Clinical Pharmacotherapy, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
| | - Yasuo Takeda
- Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
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16
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Gao L, Xu H, Ye Q, Li S, Wang J, Mei Y, Niu C, Kang T, Chen C, Wang Y. Population Pharmacokinetics and Dosage Optimization of Teicoplanin in Children With Different Renal Functions. Front Pharmacol 2020; 11:552. [PMID: 32431611 PMCID: PMC7214819 DOI: 10.3389/fphar.2020.00552] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Accepted: 04/09/2020] [Indexed: 12/12/2022] Open
Abstract
Objective The purposes of our study were to investigate the population pharmacokinetics of teicoplanin in Chinese children with different renal functions and to propose the appropriate dosing regimen for these pediatric patients. Methods We performed a prospective pharmacokinetic research on children aged 0-10 years, with different renal functions. The population pharmacokinetics model of teicoplanin was developed using NLME program. The individualized optimal dosage regimen was proposed on the basis of the obtained population pharmacokinetics parameters. Results To achieve the target trough level of 10-30 mg/L, optimal dosing regimen for children with different renal functions are predicted as follows based on the population PK simulations: children with moderate renal insufficiency need three loading doses of 6 mg/kg q12h followed by a maintenance dose of 5 mg/kg qd; children with mild renal insufficiency require three loading doses of 12 mg/kg q12h followed by a maintenance dose of 8 mg/kg qd; children with normal or augmented renal function should be given three loading doses of 12 mg/kg q12h followed by a maintenance doses of 10 mg/kg qd. Conclusion The first study on the population pharmacokinetics of teicoplanin in Chinese children with different renal functions was performed. Individualized dosing regimen was recommended for different renal function groups based on population PK model prediction.
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Affiliation(s)
- Liuliu Gao
- Department of Clinical Pharmacy, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Hua Xu
- Department of Clinical Pharmacy, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qi Ye
- Department of Clinical Pharmacy, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Sichan Li
- Department of Clinical Pharmacy, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jun Wang
- Department of Clinical Pharmacy, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yan Mei
- Department of Clinical Pharmacy, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Changhe Niu
- Department of Clinical Pharmacy, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ting Kang
- Department of Neonatology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Chen Chen
- Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yang Wang
- Department of Clinical Pharmacy, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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17
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Hahn J, Yang S, Min KL, Kim D, Jin BH, Park C, Park MS, Wi J, Chang MJ. Population pharmacokinetics of intravenous sufentanil in critically ill patients supported with extracorporeal membrane oxygenation therapy. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2019; 23:248. [PMID: 31288863 PMCID: PMC6615282 DOI: 10.1186/s13054-019-2508-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/29/2019] [Accepted: 06/06/2019] [Indexed: 01/08/2023]
Abstract
Background Sufentanil is commonly used for analgesia and sedation during extracorporeal membrane oxygenation (ECMO). Both ECMO and the pathophysiological changes derived from critical illness have significant effects on the pharmacokinetics (PK) of drugs, yet reports of ECMO and sufentanil PK are scarce. Here, we aimed to develop a population PK model of sufentanil in ECMO patients and to suggest dosing recommendations. Methods This prospective cohort PK study included 20 patients who received sufentanil during venoarterial ECMO (VA-ECMO). Blood samples were collected for 96 h during infusion and 72 h after cessation of sufentanil. A population PK model was developed using nonlinear mixed effects modelling. Monte Carlo simulations were performed using the final PK parameters with two typical doses. Results A two-compartment model best described the PK of sufentanil. In our final model, increased volume of distribution and decreased values for clearance were reported compared with previous PK data from non-ECMO patients. Covariate analysis showed that body temperature and total plasma protein level correlated positively with systemic clearance (CL) and peripheral volume of distribution (V2), respectively, and improved the model. The parameter estimates of the final model were as follows: CL = 37.8 × EXP (0.207 × (temperature − 36.9)) L h−1, central volume of distribution (V1) = 229 L, V2 = 1640 × (total plasma protein/4.5)2.46 L, and intercompartmental clearance (Q) = 41 L h−1. Based on Monte Carlo simulation results, an infusion of 17.5 μg h−1 seems to reach target sufentanil concentration (0.3–0.6 μg L−1) in most ECMO patients except hypothermic patients (33 °C). In hypothermic patients, over-sedation, which could induce respiratory depression, needs to be monitored especially when their total plasma protein level is low. Conclusions This is the first report on a population PK model of sufentanil in ECMO patients. Our results suggest that close monitoring of the body temperature and total plasma protein level is crucial in ECMO patients who receive sufentanil to provide effective analgesia and sedation and promote recovery. Trial registration Clinicaltrials.gov NCT02581280, December 1st, 2014.
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Affiliation(s)
- Jongsung Hahn
- Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon, 21983, Republic of Korea
| | - Seungwon Yang
- Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon, 21983, Republic of Korea
| | - Kyoung Lok Min
- Department of Pharmaceutical Medicine and Regulatory Sciences, Colleges of Medicine and Pharmacy, Yonsei University, Incheon, 21983, Republic of Korea
| | - Dasohm Kim
- Department of Pharmaceutical Medicine and Regulatory Sciences, Colleges of Medicine and Pharmacy, Yonsei University, Incheon, 21983, Republic of Korea.,Department of Clinical Pharmacology, Severance Hospital, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea
| | - Byung Hak Jin
- Department of Pharmaceutical Medicine and Regulatory Sciences, Colleges of Medicine and Pharmacy, Yonsei University, Incheon, 21983, Republic of Korea.,Department of Clinical Pharmacology, Severance Hospital, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea
| | - Changhun Park
- Department of Clinical Pharmacology, Severance Hospital, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea
| | - Min Soo Park
- Department of Pharmaceutical Medicine and Regulatory Sciences, Colleges of Medicine and Pharmacy, Yonsei University, Incheon, 21983, Republic of Korea.,Department of Clinical Pharmacology, Severance Hospital, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.,Department of Pediatrics, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea
| | - Jin Wi
- Division of Cardiology, Department of Internal Medicine, Gachon University Gil Medical Center, 21 Namdong-daero 774beon-gil, Namdong-gu, Incheon, 21565, Republic of Korea. .,Division of Cardiology, Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-Ro, Seodaemun-Gu, Seoul, 03722, Republic of Korea.
| | - Min Jung Chang
- Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon, 21983, Republic of Korea. .,Department of Pharmaceutical Medicine and Regulatory Sciences, Colleges of Medicine and Pharmacy, Yonsei University, Incheon, 21983, Republic of Korea.
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Ogami C, Tsuji Y, Muraki Y, Mizoguchi A, Okuda M, To H. Population Pharmacokinetics and Pharmacodynamics of Teicoplanin and C-Reactive Protein in Hospitalized Patients With Gram-Positive Infections. Clin Pharmacol Drug Dev 2019; 9:175-188. [PMID: 30934169 DOI: 10.1002/cpdd.684] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Accepted: 03/11/2019] [Indexed: 01/08/2023]
Abstract
Teicoplanin is an antibiotic agent used for the treatment of Gram-positive infections. The clinical benefit of teicoplanin is associated with its blood concentrations, but the optimal dosing regimen is not yet known. To explore the optimal individual dosing regimen, we performed a population pharmacokinetic (PK) and pharmacodynamic (PD) analysis targeting a large-scale population, including patients with a wide range of ages, body weights, and renal functions. The PK of teicoplanin was described with a 2-compartment model, and the PD of C-reactive protein (CRP) concentrations was described with a turnover maximum inhibition model. The elimination half-life of teicoplanin calculated from the final estimated parameters was 169 hours, and renal function was a significant covariate of teicoplanin clearance. The teicoplanin concentration producing 50% of the maximum inhibition of CRP production was estimated to be 2.66 mg/L. The minimum concentration of teicoplanin in patients with higher loading doses (15 mg/kg) reached the target range (15-30 mg/L) with a probability of >50% in the dosing simulation. We described the influence of body size, body composition, and renal function on the PK of teicoplanin. The population PKPD model of teicoplanin and CRP in this study should provide useful information for development of a dosing strategy including the sequential clinical benefit of teicoplanin.
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Affiliation(s)
- Chika Ogami
- Department of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama, Japan
| | - Yasuhiro Tsuji
- Department of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama, Japan
| | - Yuichi Muraki
- Department of Pharmacy, Mie University Hospital, Tsu, Japan.,Department of Clinical Pharmacoepidemiology, Kyoto Pharmaceutical University, Kyoto, Japan
| | - Akiko Mizoguchi
- Department of Pharmacy, Sasebo Chuo Hospital, Nagasaki, Japan
| | - Masahiro Okuda
- Department of Pharmacy, Mie University Hospital, Tsu, Japan
| | - Hideto To
- Department of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Toyama, Toyama, Japan
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Mikamo H, Takesue Y, Iwamoto Y, Tanigawa T, Kato M, Tanimura Y, Kohno S. Efficacy, safety and pharmacokinetics of tedizolid versus linezolid in patients with skin and soft tissue infections in Japan – Results of a randomised, multicentre phase 3 study. J Infect Chemother 2018. [DOI: 10.1016/j.jiac.2018.01.010] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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Kasai H, Tsuji Y, Hiraki Y, Tsuruyama M, To H, Yamamoto Y. Population pharmacokinetics of teicoplanin in hospitalized elderly patients using cystatin C as an indicator of renal function. J Infect Chemother 2017; 24:284-291. [PMID: 29292178 DOI: 10.1016/j.jiac.2017.12.002] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Revised: 11/20/2017] [Accepted: 12/04/2017] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Serum cystatin C (CysC) has recently been proposed as an alternative marker to serum creatinine (SCR) for estimating renal clearance. In the present study, we performed a population pharmacokinetic analysis of teicoplanin (TEIC), which is mainly eliminated through the kidneys, using CysC as a predictor for renal clearance. METHODS Thirty-six patients with MRSA infections who were administrated to the National Hospital Organization Beppu Medical Center between January 2012 and December 2013 were enrolled and gave 123 sets of blood TEIC concentration data. Renal clearance was estimated by the Hoek equation using CysC, by creatinine clearance predicted by the Cockcroft-Gault equation using SCR, or directly by CysC. One compartment open model with inter-individual variabilities for renal clearance and the volume of distribution as well as an additional residual error model was used to estimate population pharmacokinetic parameters for TEIC. RESULTS The model with the best predictability was that with CysC as a predictor for renal clearance; it showed better significance than the models using estimated the glomerular filtration rate by the Hoek equation or CLcr. The final model was as follows: CL (L/hr) = 0.510 × (CysC/1.4)-0.68 × Total body weight/600.81, omega (CL) = 19.8% CV, VC (L) = 78.1, omega (V) = 42.7% CV. CONCLUSION The present results show the usefulness of CysC to more accurately predict the pharmacokinetics of drugs mainly eliminated through the kidneys, such as TEIC. However, since the sample size in this study was relatively small, further investigations on renal clearance predictability using CysC are needed.
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Affiliation(s)
- Hidefumi Kasai
- Department of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan; Certara G.K., 4-2-12, Minato-ku, Tokyo, 105-0001, Japan
| | - Yasuhiro Tsuji
- Department of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan.
| | - Yoichi Hiraki
- Department of Pharmacy, National Hospital Organization Beppu Medical Center, 1473 Uchikamado, Beppu, Oita, 874-0011, Japan
| | - Moeko Tsuruyama
- Department of Pharmacy, National Hospital Organization Beppu Medical Center, 1473 Uchikamado, Beppu, Oita, 874-0011, Japan
| | - Hideto To
- Department of Medical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan
| | - Yoshihiro Yamamoto
- Department of Clinical Infectious Diseases, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan
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Population Pharmacokinetics and Dose Optimization of Teicoplanin during Venoarterial Extracorporeal Membrane Oxygenation. Antimicrob Agents Chemother 2017; 61:AAC.01015-17. [PMID: 28674057 DOI: 10.1128/aac.01015-17] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2017] [Accepted: 06/24/2017] [Indexed: 12/14/2022] Open
Abstract
The pharmacokinetics (PK) of drugs are known to be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). However, clinical studies of the PK of drugs administered during ECMO are scarce, and the proper dosing adjustment has yet to be established. We developed a population PK model for teicoplanin, investigated covariates influencing teicoplanin exposure, and suggested an optimal dosing regimen for ECMO patients. Samples for PK analysis were collected from 10 adult patients, and a population PK analysis and simulations were performed to identify an optimal teicoplanin dose needed to provide a >50% probability of target attainment at 72 h using a trough concentration target of >10 μg/ml for mild to moderate infections and a trough concentration target of >15 μg/ml for severe infections. Teicoplanin was well described by a two-compartment PK model with first-order elimination. The presence of ECMO was associated with a lower central volume of distribution, and continuous renal replacement therapy (CRRT) was associated with a higher peripheral volume of distribution. For mild to moderate infections, an optimal dose was a loading dose (LD) of 600 mg and a maintenance dose (MD) of 400 mg for ECMO patients not receiving CRRT and an LD of 800 mg and an MD of 600 mg for those receiving CRRT. For severe infections, an optimal dose was an LD of 1,000 mg and an MD of 800 mg for ECMO patients not receiving CRRT and an LD of 1,200 mg and an MD of 1,000 mg for those receiving CRRT. In conclusion, doses higher than the standard doses are needed to achieve fast and appropriate teicoplanin exposure during ECMO. (This study has been registered at ClinicalTrials.gov under identifier NCT02581280.).
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Cazaubon Y, Venisse N, Mimoz O, Maire P, Ducher M, Bourguignon L, Goutelle S. Population pharmacokinetics of teicoplanin administered by subcutaneous or intravenous route and simulation of optimal loading dose regimen. J Antimicrob Chemother 2017; 72:2804-2812. [DOI: 10.1093/jac/dkx242] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Accepted: 06/19/2017] [Indexed: 12/16/2022] Open
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Li N, Zhu L, Xu G, Ge T, Qi F, Li M. Optimal teicoplanin dosage regimens for methicillin-resistant Staphylococcus aureus infections in endocarditis patients and renal failure patients. J Chemother 2017; 29:358-364. [PMID: 28587526 DOI: 10.1080/1120009x.2017.1334031] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
This study aimed to assess whether traditional initial loading and maintenance doses of teicoplanin were appropriate in endocarditis and renal failure patients with methicillin-resistant Staphylococcus aureus (MRSA) infections and to recommend optimal dosage regimens. Pharmacokinetic parameters and physicochemical properties of teicoplanin were performed to develop pharmacokinetic models using GastroPlusTM. Concentration-time curves of teicoplanin in endocarditis and renal failure patients with MRSA infections were simulated by changing clearance (CL) and volume of distribution of the central compartment (Vc). Different teicoplanin dosage regimens were assessed according to the target trough concentration, and optimal teicoplanin dosage regimens were recommended. Dosage regimen of four teicoplanin doses of 6 mg/kg q12 h followed by 6 mg/kg qd is recommended for renal failure patients infected by MRSA. And optimal dosage regimen is five teicoplanin doses of 15 mg/kg q12 h followed by doses of 12 mg/kg qd for endocarditis patients infected by MRSA.
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Affiliation(s)
- Na Li
- a Department of Clinical Pharmacy , Tianjin Medical University , Tianjin , China
| | - Liqin Zhu
- b Department of Pharmacy , Tianjin First Central Hospital , Tianjin , China
| | - Gaoqi Xu
- c Department of Pharmacology , Tianjin Medical University , Tianjin , China
| | - Tingyue Ge
- c Department of Pharmacology , Tianjin Medical University , Tianjin , China
| | - Fang Qi
- a Department of Clinical Pharmacy , Tianjin Medical University , Tianjin , China
| | - Mengxue Li
- a Department of Clinical Pharmacy , Tianjin Medical University , Tianjin , China
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Kato H, Hamada Y, Hagihara M, Hirai J, Nishiyama N, Koizumi Y, Yamagishi Y, Matsuura K, Mikamo H. Retrospective study of teicoplanin loading regimen that rapidly achieves target 15–30 μg/mL serum trough concentration. J Infect Chemother 2016; 22:308-13. [DOI: 10.1016/j.jiac.2016.01.019] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2015] [Revised: 01/21/2016] [Accepted: 01/22/2016] [Indexed: 11/26/2022]
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Matsumoto K, Watanabe E, Kanazawa N, Fukamizu T, Shigemi A, Yokoyama Y, Ikawa K, Morikawa N, Takeda Y. Pharmacokinetic/pharmacodynamic analysis of teicoplanin in patients with MRSA infections. Clin Pharmacol 2016; 8:15-8. [PMID: 27099534 PMCID: PMC4822798 DOI: 10.2147/cpaa.s96143] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background Teicoplanin is a glycopeptide antibiotic that has been used to treat serious, invasive infections caused by Gram-positive bacteria. The area under the drug concentration–time curve (AUC)/minimum inhibitory concentration (MIC) was identified as a pharmacokinetic–pharmacodynamic (PK–PD) parameter of glycopeptide antibiotics that correlated with bacteriological responses and clinical outcomes. Although optimized dosing regimens based on PK–PD are needed, a PK–PD analysis of teicoplanin against methicillin-resistant Staphylococcus aureus (MRSA) infections has not yet been performed. Thus, this study examined patients with MRSA infections, who were administered with teicoplanin in order to determine the target AUC/MIC ratio. Methods This study retrospectively assessed data obtained as part of our routine therapeutic drug monitoring (TDM) of teicoplanin therapy in 46 patients with MRSA infections at Kagoshima University Hospital. Serum concentrations of teicoplanin were determined using a fluorescence polarization immunoassay system and used for a Bayesian PK estimation to estimate AUC for 24 hours (AUC24). The MIC value for teicoplanin was determined using a standardized agar dilution method. The effects of teicoplanin were evaluated in terms of bacteriological responses by a quantitative assessment. Results The estimated AUC24/MIC ratios with and without bacteriological responses were 926.6±425.2 µg·h/mL (n=34) and 642.2±193.9 µg·h/mL, respectively (n=12; P<0.05). On the basis of a logistic regression analysis, AUC24/MIC ratios of 500 µg·h/mL, 700 µg·h/mL, and 900 µg·h/mL gave probabilities of treatment success of 0.50, 0.72, and 0.87, respectively. Furthermore, using the Kaplan–Meier curve analysis, an AUC24/MIC ratio of ≥900 led to a significantly stronger bacteriological response than an AUC24/MIC ratio of <900. Conclusion These results suggest that an AUC24/MIC ratio of ≥900 µg·h/mL is required to ensure a sufficient bacteriological response.
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Affiliation(s)
- Kazuaki Matsumoto
- Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Erika Watanabe
- Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Naoko Kanazawa
- Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Tomohide Fukamizu
- Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Akari Shigemi
- Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
| | - Yuta Yokoyama
- Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan; Department of Clinical Pharmacotherapy, Hiroshima University, Hiroshima, Japan
| | - Kazuro Ikawa
- Department of Clinical Pharmacotherapy, Hiroshima University, Hiroshima, Japan
| | - Norifumi Morikawa
- Department of Clinical Pharmacotherapy, Hiroshima University, Hiroshima, Japan
| | - Yasuo Takeda
- Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
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Tsai D, Jamal JA, Davis JS, Lipman J, Roberts JA. Interethnic differences in pharmacokinetics of antibacterials. Clin Pharmacokinet 2015; 54:243-60. [PMID: 25385446 DOI: 10.1007/s40262-014-0209-3] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Optimal antibacterial dosing is imperative for maximising clinical outcome. Many factors can contribute to changes in the pharmacokinetics of antibacterials to the extent where dose adjustment may be needed. In acute illness, substantial changes in important pharmacokinetic parameters such as volume of distribution and clearance can occur for certain antibacterials. The possibility of interethnic pharmacokinetic differences can further complicate attempts to design an appropriate dosing regimen. Factors of ethnicity, such as genetics, body size and fat distribution, contribute to differences in absorption, distribution, metabolism and elimination of drugs. Despite extensive previous work on the altered pharmacokinetics of antibacterials in some patient groups such as the critically ill, knowledge of interethnic pharmacokinetic differences for antibacterials is limited. OBJECTIVES This systematic review aims to describe any pharmacokinetic differences in antibacterials between different ethnic groups, and discuss their probable mechanisms as well as any clinical implications. METHODS We performed a structured literature review to identify and describe available data of the interethnic differences in the pharmacokinetics of antibacterials. RESULTS We found 50 articles that met our inclusion criteria and only six of these compared antibacterial pharmacokinetics between different ethnicities within the same study. Overall, there was limited evidence available. We found that interethnic pharmacokinetic differences are negligible for carbapenems, most β-lactams, aminoglycosides, glycopeptides, most fluoroquinolones, linezolid and daptomycin, whereas significant difference is likely for ciprofloxacin, macrolides, clindamycin, tinidazole and some cephalosporins. In general, subjects of Asian ethnicity achieve drug exposures up to two to threefold greater than Caucasian counterparts for these antibacterials. This difference is caused by a comparatively lower volume of distribution and/or drug clearance. CONCLUSION Interethnic pharmacokinetic differences of antibacterials are likely; however, the clinical relevance of these differences is unknown and warrants further research.
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Affiliation(s)
- Danny Tsai
- Burns, Trauma and Critical Care Research Centre, School of Medicine, The University of Queensland, Level 3, Ned Hanlon Building, Royal Brisbane and Women's Hospital, Herston, Brisbane, QLD, 4029, Australia
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Enokiya T, Muraki Y, Iwamoto T, Okuda M. Changes in the pharmacokinetics of teicoplanin in patients with hyperglycaemic hypoalbuminaemia: Impact of albumin glycosylation on the binding of teicoplanin to albumin. Int J Antimicrob Agents 2015; 46:164-8. [PMID: 25982916 DOI: 10.1016/j.ijantimicag.2015.03.010] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2014] [Revised: 02/20/2015] [Accepted: 03/08/2015] [Indexed: 11/25/2022]
Abstract
There is large interindividual variability in serum teicoplanin (TEIC) concentrations after administration of a loading dose, and the factors that influence the pharmacokinetics of TEIC are disputed. The aim of this study was to clarify changes in the pharmacokinetics of TEIC that occur in patients with hyperglycaemia as well as the impact of albumin glycosylation on the pharmacokinetics of TEIC. This study consisted of retrospective and prospective investigations. The pharmacokinetic parameters of TEIC were retrospectively compared between patients receiving TEIC treatment. Ninety-four patients were divided into four groups according to their serum albumin and blood glucose concentrations [(i) hyperglycaemic hypoalbuminaemia (albumin<3.0g/dL) (n=16); (ii) non-hyperglycaemic hypoalbuminaemia (n=29); (iii) hyperglycaemic normoalbuminaemia (albumin≥3.0g/dL) (n=9); and (iv) non-hyperglycaemic normoalbuminaemia (n=40)]. In addition, the concentration of glycosylated albumin was prospectively determined in 28 patients. At 12h after administration of a loading dose, patients with hyperglycaemic hypoalbuminaemia displayed significantly lower serum TEIC concentrations (P<0.05) and higher TEIC volume of distribution (Vd) (P<0.05) than the other three groups, whereas TEIC clearance did not differ significantly among the groups. In addition, the percentage of glycosylated albumin was significantly correlated with the association constant (Ka) of TEIC for albumin (r=0.53, P=0.004) and the Vd (r=0.41, P=0.031). These results suggest that hyperglycaemic hypoalbuminaemia lowers the serum TEIC concentration, which is attributable to the decreased Ka and increased Vd of TEIC by albumin glycosylation.
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Affiliation(s)
- Tomoyuki Enokiya
- Department of Pharmacy, Mie University Hospital, Faculty of Medicine, Mie University, 2-174 Edobashi, Tsu 514-8507, Mie, Japan
| | - Yuichi Muraki
- Department of Pharmacy, Mie University Hospital, Faculty of Medicine, Mie University, 2-174 Edobashi, Tsu 514-8507, Mie, Japan
| | - Takuya Iwamoto
- Department of Pharmacy, Mie University Hospital, Faculty of Medicine, Mie University, 2-174 Edobashi, Tsu 514-8507, Mie, Japan
| | - Masahiro Okuda
- Department of Pharmacy, Mie University Hospital, Faculty of Medicine, Mie University, 2-174 Edobashi, Tsu 514-8507, Mie, Japan.
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