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Szalai G, Katona G, Matuz M, Jójárt-Laczkovich O, Doró P. Physical compatibility of MCT/LCT propofol emulsions with crystalloids during simulated Y-site administration. Eur J Hosp Pharm 2019; 25:e139-e143. [PMID: 31157085 DOI: 10.1136/ejhpharm-2017-001374] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2017] [Revised: 11/27/2017] [Accepted: 12/06/2017] [Indexed: 11/04/2022] Open
Abstract
Objective In intensive care units numerous drugs have to be infused simultaneously, resulting inline incompatibility. Propofol is formulated as a lipid emulsion and it is well known that electrolytes can affect the stability of an emulsion system. Our goal was to evaluate and to compare the physical compatibility of three commercial propofol lipid emulsions of different manufacturers, mixing them with the most commonly used crystalloids in intensive care units. Methods Simulated Y-site administration was accomplished by mixing the 2% MCT/LCT propofol emulsions with the commonly used crystalloids in the intensive care unit in a 1:1 ratio in a polypropylene syringe. The aliquot samples were evaluated immediately and at 15, 30, 60 and 120 min after preparation by visual observation, pH and droplet size measurement. Results There was no emulsion breakdown or any visible change during the study period. Mixing the propofols with crystalloids, 10% magnesium sulphate or 10% potassium chloride there was no significant change in the droplet size compared with the original propofol emulsions. A slight alteration in droplet size was noticed in a few of the propofol samples, when magnesium, potassium or both were the secondary additives to the crystalloids, but this is not considered clinically relevant. Conclusion The physical properties of emulsions are determined by component, therefore the compatibility data in literature has to be evaluated prudently. All three commercially available MCT/LCT propofol emulsions are considered physically compatible with the tested crystalloids.
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Affiliation(s)
- Gábor Szalai
- Department of Clinical Pharmacy, University of Szeged Faculty of Pharmacy, Szeged, Hungary
| | - Gábor Katona
- Department of Pharmaceutical Technology and Drug Regulatory Affairs, University of Szeged Faculty of Pharmacy, Szeged, Hungary
| | - Mária Matuz
- Department of Clinical Pharmacy, University of Szeged Faculty of Pharmacy, Szeged, Hungary
| | - Orsolya Jójárt-Laczkovich
- Department of Pharmaceutical Technology and Drug Regulatory Affairs, University of Szeged Faculty of Pharmacy, Szeged, Hungary
| | - Péter Doró
- Department of Clinical Pharmacy, University of Szeged Faculty of Pharmacy, Szeged, Hungary
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Singla B, Malde AD. A prospective observational study of injection pain in children with medium plus long chain triglyceride and long chain triglyceride propofol premixed with lignocaine. Indian J Anaesth 2018; 62:214-218. [PMID: 29643556 PMCID: PMC5881324 DOI: 10.4103/ija.ija_506_17] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
Background and Aims: Propofol injection pain is an unresolved problem in children. Although medium and long chain triglyceride (MCT-LCT) propofol has shown promising results in adults, its efficacy in children is not proven. In a prospective observational study the incidence and severity of pain with MCT-LCT and LCT propofol in children was compared. Methods: After obtaining approval from the Institutional Ethics Committee, 170 children (age group 6 months to 8 years) scheduled for various surgeries were included in this study. Following standard pre-medication, propofol 1% either LCT or MCT-LCT in a dose of 2–4 mg/kg along with preservative-free lignocaine (2% lignocaine 1 mg in propofol 10 mg) was administered. The primary objective was to study injection pain on scale of 0–6. For children ≤2 years doubling of motor event score (0–3) and for children >2 years, addition of motor (0–3) and verbalisation scores (0–3) were considered. Mann–Whitney U test was used for statistical analysis. Results: MCT-LCT group had lower incidence of pain (17 patients (20%) versus 35 patients (35.3%), P = 0.026) and severe pain (zero patients (0%) versus six patients (7.1%), P = 0.029) as compared to LCT group. MCT-LCT group had significantly lower mean rank of motor (79.65 versus 91.35), verbal (77.29 versus 90.79) and total score (77.76 versus 93.24) as compared to LCT group (P = 0.037, 0.002, and 0.009, respectively). Conclusion: MCT-LCT propofol is associated with significantly lower injection pain as compared to LCT propofol in children, when both are combined with lignocaine.
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Affiliation(s)
- Bhavika Singla
- Department of Anesthesiology, LTMMC, LTMGH, Mumbai, Maharashtra, India
| | - Anila D Malde
- Department of Anesthesiology, LTMMC, LTMGH, Mumbai, Maharashtra, India
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3
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Lee M, Kwon T, Kim S, Kim S, Park K, Jeon Y. Comparative evaluation of the effect of remifentanil and 2 different doses of esmolol on pain during propofol injection: A double-blind, randomized clinical consort study. Medicine (Baltimore) 2017; 96:e6288. [PMID: 28272252 PMCID: PMC5348200 DOI: 10.1097/md.0000000000006288] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Propofol is associated with pain during injection, which is stressful to patients. The present study was designed to investigate the analgesic effect of pretreatment with remifentanil and esmolol in minimizing propofol injection pain, compared with placebo. METHODS In a randomized, double-blind, prospective trial, 120 patients, scheduled for elective dental surgery under general anesthesia, were randomized to 1 of the 4 treatment arms (n = 30 each) receiving normal saline, remifentanil 0.35 μg/kg, esmolol 0.5 mg/kg, and 1 mg/kg before administration of propofol. During injection of 1% propofol 0.5 mg/kg, pain was evaluated by a 4-point score (0 = none, 1 = mild, 2 = moderate, 3 = severe). Any adverse effects such as hypotension and bradycardia were recorded during the perioperative periods. RESULTS In all, 120 patients completed this study. There were no significant differences in terms of demographic data. The incidence of pain on injection of propofol was 11 (36.7%) with remifentanil 0.35 μg/kg, 12 (40%) with esmolol 0.5 mg/kg, and 11 (36.7%) with esmolol 1 mg/kg, compared with 25 (83.3%) with normal saline (respectively, P < 0.05). There were no significant differences in the incidence of pain between groups with remifentanil 0.35 μg/kg, and esmolol 0.5 mg/kg and 1 mg/kg. There were no emergence reactions such as hypotension and bradycardia in all groups. CONCLUSIONS Pretreatment with esmolol 0.5 mg/kg and 1 mg/kg and remifentanil 0.35 μg/kg equally decreased pain during propofol injection.
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Affiliation(s)
- Myunghwan Lee
- Department of Oral and Maxillofacial surgery, School of Dentistry
| | - Taegeon Kwon
- Department of Oral and Maxillofacial surgery, School of Dentistry
| | - Sujin Kim
- Department of Anesthesiology and Pain Medicine, Kyungpook National University Hospital
| | - Saeyoung Kim
- Department of Anesthesiology and Pain Medicine, Kyungpook National University Hospital
| | - Kibum Park
- Department of Anesthesiology and Pain Medicine, Keimyung University Dongsan Hospital, Daegu, Republic of Korea
| | - Younghoon Jeon
- Department of Oral and Maxillofacial surgery, School of Dentistry
- Department of Anesthesiology and Pain Medicine, Kyungpook National University Hospital
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Feng AY, Kaye AD, Kaye RJ, Belani K, Urman RD. Novel propofol derivatives and implications for anesthesia practice. J Anaesthesiol Clin Pharmacol 2017; 33:9-15. [PMID: 28413268 PMCID: PMC5374837 DOI: 10.4103/0970-9185.202205] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Propofol (2,6-diisopropylphenol) is the most commonly used intravenous agent for induction of anesthesia. It is also used for maintenance of anesthesia and sedation in both Intensive Care Units and outpatient procedural settings. Its success in the clinical setting has been a result of its rapid onset, short duration of action, and minimal side effects despite disadvantages associated with its oil emulsion formulation. Early attempts to alter the standard emulsion or to develop new formulations with cyclodextrins and micelles to resolve issues with pain upon injection, the need for antimicrobial agents, and possible hyperlipidemia have mostly failed. With these challenges in the foreground, attention has now shifted to the use of more prodrugs and exogenous alternatives, the success of which is yet to be determined. These new agents must offer significant clinical advantages over the well-entrenched, generic propofol oil emulsion to justify higher costs and to be well received in the increasingly cost-conscious healthcare marketplace.
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Affiliation(s)
- Aiden Y Feng
- Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - Alan D Kaye
- Department of Anesthesiology and Pharmacology, Louisiana State University Health Sciences Center, New Orleans, LA, USA
| | - Rachel J Kaye
- Department of Anesthesiology and Pharmacology, Louisiana State University Health Sciences Center, New Orleans, LA, USA.,Department of Biochemistry, Bowdoin College, Brunswick, ME, USA
| | - Kumar Belani
- Department of Anesthesiology, University of Minnesota, Minneapolis, MN, USA
| | - Richard D Urman
- Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, MA, USA
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Abstract
Pain on propofol injection (POPI) is a minor problem that all anesthetists face every day. Introduction of several new formulations and hundreds of clinical trials have failed to find its remedy with just one intervention in all patients. This article highlights the causes of POPI and interventions that are used to eliminate this pain in current practice. Relevant articles from Medline and Embase databases were searched and included in this descriptive review with the following conclusions: (1) POPI is due to irritation of venous adventitia leading to release of mediators such as kininogen from kinin cascade. (2) When two or more drugs or measures are used, the incidence of POPI decreases considerably. Hence, the approach to eliminating POPI should be multimodal. (3) Any regimen that includes a drug having local anesthetic effect combined with central sedative/analgesic and rapid injection into a large vein should definitely reduce the risk of POPI to negligible levels.
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Yoo JH, Kim YI, Kim SI, Lee SJ, Han YM. Evaluation of palonosetron for the prevention of pain on injection of LCT/MCT propofol: Randomized controlled comparison with lidocaine. Anesth Pain Med (Seoul) 2016. [DOI: 10.17085/apm.2016.11.3.249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Affiliation(s)
- Jae-Hwa Yoo
- Department of Anesthesiology and Pain Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - Yong Ik Kim
- Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Soon Im Kim
- Department of Anesthesiology and Pain Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - Se-Jin Lee
- Department of Anesthesiology and Pain Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea
| | - Yoo-mi Han
- Department of Anesthesiology and Pain Medicine, Soonchunhyang University Seoul Hospital, Seoul, Korea
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The Influence of Differences in Solvents and Concentration on the Efficacy of Propofol at Induction of Anesthesia. Anesthesiol Res Pract 2016; 2016:9178523. [PMID: 26904114 PMCID: PMC4745982 DOI: 10.1155/2016/9178523] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2015] [Revised: 01/05/2016] [Accepted: 01/10/2016] [Indexed: 11/18/2022] Open
Abstract
Background. Propofol is a popular intravenous anesthetic and varieties of formulations were produced from different laboratories. The present study compared efficacy of propofol of different laboratories and different concentrations (1 and 2%) during induction of anesthesia. Methods. Seventy-five scheduled surgical patients were randomly allocated into three groups. The patients of group D1 received AstraZeneca Diprivan 1% (Osaka, Japan) at a rate of 40 mg kg−1 h−1. Group M1 was given 1% Maruishi (Maruishi Pharmaceutical, Osaka, Japan) and group M2 was given 2% formulation at the same rate of propofol. Achieving hypnosis was defined as failure to open their eyes in response to a verbal command and the venous blood sample was withdrawn. Results. The hypnotic doses of M2 were significantly larger (D1: 91.4 ± 30.9, M1: 90.7 ± 26.7, and M2: 118.4 ± 40.2 mg, resp. (mean ± SD). p < 0.005). Age and gender were selected as statistically significant covariates using general linear model-ANOVA. The blood concentration showed no significant difference among the groups (3.73 ± 2.34, 4.10 ± 3.04, and 4.70 ± 2.12 μg mL−1, resp.). Conclusion. The required dose of propofol was different among the formulations; however, the serum concentration showed no significant difference. This trial is registered with UMIN Clinical Trial Registry: UMIN000019925.
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Amornyotin S. Registered nurse-administered sedation for gastrointestinal endoscopic procedure. World J Gastrointest Endosc 2015; 7:769-76. [PMID: 26191341 PMCID: PMC4501967 DOI: 10.4253/wjge.v7.i8.769] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2014] [Revised: 12/24/2014] [Accepted: 05/05/2015] [Indexed: 02/05/2023] Open
Abstract
The rising use of nonanesthesiologist-administered sedation for gastrointestinal endoscopy has clinical significances. Most endoscopic patients require some forms of sedation and/or anesthesia. The goals of this sedation are to guard the patient's safety, minimize physical discomfort, to control behavior and to diminish psychological responses. Generally, moderate sedation for these procedures has been offered by the non-anesthesiologist by using benzodiazepines and/or opioids. Anesthesiologists and non-anesthesiologist personnel will need to work together for these challenges and for safety of the patients. The sedation training courses including clinical skills and knowledge are necessary for the registered nurses to facilitate the patient safety and the successful procedure. However, appropriate patient selection and preparation, adequate monitoring and regular training will ensure that the use of nurse-administered sedation is a feasible and safe technique for gastrointestinal endoscopic procedures.
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Byon HJ, Lee KW, Shim HY, Song JH, Jung JK, Cha YD, Lee DI. Comparison of the preventive effects of pretreatment of lidocaine with a tourniquet and a premixed injection of lidocaine on propofol-LCT/MCT injection pain. Korean J Anesthesiol 2014; 66:95-8. [PMID: 24624265 PMCID: PMC3948449 DOI: 10.4097/kjae.2014.66.2.95] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2013] [Revised: 07/02/2013] [Accepted: 08/08/2013] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Lidocaine has been used widely to prevent propofol injection pain. Various methods of administration exist, such as lidocaine premixed with propofol or lidocaine pretreatment using a tourniquet, but it is unclear which method of lidocaine administration is more effective for the prevention of injection pain of propofol LCT/MCT. The purpose of this study was to compare pretreatment of lidocaine with a tourniquet and a premixed injection of lidocaine to prevent injection pain of propofol-LCT/MCT. METHODS Patients were randomly allocated into the pretreatment group (n = 117) or the premixed group (n = 117). The pretreatment group was pretreated with 2 ml of lidocaine 2%, held with a tourniquet, before propofol-LCT/MCT injection. The premixed group was injected with a premixed solution of propofol-LCT/MCT and 2 ml of lidocaine 2%. To evaluate the incidence and severity of pain, spontaneous verbal expressions of pain, movement of hand, frowning, and moaning were recorded, and the patients were asked to recall their pain with the visual analogue score (VAS) 30 minutes after awakening from anesthesia. RESULTS Overall, injection pain occurred in 13.7% of the pretreatment group and 15.4% of the premixed group, without any statistical difference (P = 0.71). There was no difference in spontaneous verbal expressions of pain, movement of hand, frowning, and moaning between the two groups. The pain intensity (VAS) also showed no difference between the two groups (P = 0.49). CONCLUSIONS Pretreatment of lidocaine with a tourniquet showed no more benefit to prevent injection pain of propofol LCT/MCT compared to a premixed injection with lidocaine.
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Affiliation(s)
- Hyo Jin Byon
- Department of Anesthesiology and Pain Medicine, Inha University College of Medicine, Incheon, Korea
| | - Kil Woo Lee
- Department of Anesthesiology and Pain Medicine, Inha University College of Medicine, Incheon, Korea
| | - Hee Yong Shim
- Department of Anesthesiology and Pain Medicine, Inha University College of Medicine, Incheon, Korea
| | - Jang Ho Song
- Department of Anesthesiology and Pain Medicine, Inha University College of Medicine, Incheon, Korea
| | - Jong Kwon Jung
- Department of Anesthesiology and Pain Medicine, Inha University College of Medicine, Incheon, Korea
| | - Young Deog Cha
- Department of Anesthesiology and Pain Medicine, Inha University College of Medicine, Incheon, Korea
| | - Doo Ik Lee
- Department of Anesthesiology and Pain Medicine, Inha University College of Medicine, Incheon, Korea
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10
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Gill KL, Gertz M, Houston JB, Galetin A. Application of a physiologically based pharmacokinetic model to assess propofol hepatic and renal glucuronidation in isolation: utility of in vitro and in vivo data. Drug Metab Dispos 2013; 41:744-53. [PMID: 23303442 PMCID: PMC3608455 DOI: 10.1124/dmd.112.050294] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2012] [Accepted: 01/09/2013] [Indexed: 11/22/2022] Open
Abstract
A physiologically based pharmacokinetic (PBPK) modeling approach was used to assess the prediction accuracy of propofol hepatic and extrahepatic metabolic clearance and to address previously reported underprediction of in vivo clearance based on static in vitro-in vivo extrapolation methods. The predictive capacity of propofol intrinsic clearance data (CLint) obtained in human hepatocytes and liver and kidney microsomes was assessed using the PBPK model developed in MATLAB software. Microsomal data obtained by both substrate depletion and metabolite formation methods and in the presence of 2% bovine serum albumin were considered in the analysis. Incorporation of hepatic and renal in vitro metabolic clearance in the PBPK model resulted in underprediction of propofol clearance regardless of the source of in vitro data; the predicted value did not exceed 35% of the observed clearance. Subsequently, propofol clinical data from three dose levels in intact patients and anhepatic subjects were used for the optimization of hepatic and renal CLint in a simultaneous fitting routine. Optimization process highlighted that renal glucuronidation clearance was underpredicted to a greater extent than liver clearance, requiring empirical scaling factors of 17 and 9, respectively. The use of optimized clearance parameters predicted hepatic and renal extraction ratios within 20% of the observed values, reported in an additional independent clinical study. This study highlights the complexity involved in assessing the contribution of extrahepatic clearance mechanisms and illustrates the application of PBPK modeling, in conjunction with clinical data, to assess prediction of clearance from in vitro data for each tissue individually.
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Affiliation(s)
- Katherine L Gill
- Centre for Applied Pharmacokinetic Research, School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT, UK
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Beyaz SG, Eman A. Injection pain of propofol in children: A comparison of two formulations without added lidocaine. J Anaesthesiol Clin Pharmacol 2012; 28:314-7. [PMID: 22869935 PMCID: PMC3409938 DOI: 10.4103/0970-9185.98322] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Background: Propofol emulsion in medium and long-chain triglycerides (MCT/LCT) has been reported to cause less injection pain than other propofol solutions in adult studies. The aim of this study was to compare the injection pain of two different propofol emulsions using two different pain scales on the pediatric population. Materials and Methods: 100 children scheduled for general anesthesia were divided into two groups. Patients were randomly assigned to receive propofol LCT or propofol MCT/LCT. Assessment and evaluation of the Ontario Children's Hospital Pain Scale (mCHEOPS) and the Wong-Baker Faces Scale (WBFS) were performed at the start of the injection until the patients lose consciousness. Results: There were no significant differences between groups in terms of demographic data. According to the mCHEOPS scale, the pain incidence of propofol LCT was 5%, whereas for propofol MCT/LCT it was 15% (P < 0.05). According to the WBFS Pain Scale, the pain incidence of propofol LCT was 17%, whereas for propofol MCT/LCT it was 21% (P > 0.05). Conclusions: Propofol MCT/LCT does not decrease injection pain; contrary to the general assumption, it causes more pain than propofol LCT in children.
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Affiliation(s)
- Serbülent Gökhan Beyaz
- Department of Anaesthesiology, Sakarya University Medical School, Sakarya, Republic of Turkey
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12
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Buggins TR, Dickinson PA, Taylor G. The effects of pharmaceutical excipients on drug disposition. Adv Drug Deliv Rev 2007; 59:1482-503. [PMID: 18198495 DOI: 10.1016/j.addr.2007.08.017] [Citation(s) in RCA: 71] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Many new chemical entities are poorly soluble, requiring the use of co-solvents or excipients to produce suitable intravenous formulations for early pre-clinical development studies. There is some evidence in the literature that these formulation components can have significant physiological and physicochemical effects which may alter the distribution and elimination of co-administered drugs. Such effects have the potential to influence the results of pre-clinical pharmacokinetic studies, giving a false impression of a compound's intrinsic pharmacokinetics and frustrating attempts to predict the drug's ultimate clinical pharmacokinetics. This review describes the reported effects of commonly used co-solvents and excipients on drug pharmacokinetics and on physiological systems which are likely to influence drug disposition. Such information will be useful in study design and evaluating data from pharmacokinetic experiments, so that the potential influence of formulation components can be minimised.
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13
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Redondo García JI. Clinical evaluation of a new formulation of propofol in a medium-chain and long-chain triglycerides emulsion in dogs. J Vet Pharmacol Ther 2007; 30:288-94. [PMID: 17610401 DOI: 10.1111/j.1365-2885.2007.00859.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Propofol formulated in a mixed medium-chain and long-chain triglycerides emulsion has been recently introduced for clinical use as an alternative to the conventional long-chain triglycerides formulation. This prospective multicentric study evaluated the clinical effectiveness and the complications associated with the use of this new formulation of propofol in dogs. Forty-six Spanish veterinary clinics participated in this study. A total of 541 anaesthesias (118 ASA I, 290 ASA II, 101 ASA III and 32 ASA IV) performed for various diagnostic and therapeutic purposes were evaluated. The anaesthetic protocol was not controlled, with the exception that propofol had to be used at least for induction of anaesthesia. The induction dose of propofol and the incidence of anaesthetic complications throughout the procedure were recorded. A chi-square test compared the incidence of complications according to the maintenance agent used (propofol vs. inhalatory anaesthesia), anaesthetic risk (ASA classification) and the reason for the anaesthesia. The patients premedicated with alpha2 agonists needed lower doses (mean +/- SD, 2.9 +/- 1.3 mg/kg i.v.) than the animals premedicated with phenothiazines (3.9 +/- 1.4 mg/kg i.v.) or benzodiazepines (4.0 +/- 1.4 mg/kg i.v.). The most frequent complications were difficult endotracheal intubation (1.3%), postinduction apnoea (11.3%), cyanosis (0.6%), bradypnoea (2.6%), tachypnoea (2.8%), bradycardia (2%), tachycardia (2.6%), hypotension (0.2%), shock (0.2%), vomiting (4.6%), epileptiform seizures (2.8%), premature awakening (7.4%) and delayed recovery (0.9%). There were no cases of pain on injection or aspiration pneumonia. Three dogs died (0.55%), one during induction and two during recovery from anaesthesia. This study demonstrates that the new formulation of propofol is an useful and effective drug to induce general anaesthesia in dogs.
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Affiliation(s)
- J I Redondo García
- Dpto. Medicina y Cirugía Animal, Universidad CEU Cardenal Herrera, Moncada, Valencia, Spain.
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Liljeroth E, Karlsson A, Lagerkranser M, Akeson J. Sustained intravascular exposure to propofol does not prolong pain at the site of injection. Acta Anaesthesiol Scand 2007; 51:456-9. [PMID: 17378784 DOI: 10.1111/j.1399-6576.2006.01256.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND Pain at the site of intravenous injection of propofol is a common clinical finding. This double-blind, randomized cross-over study was designed to evaluate whether venous occlusion applied during injection of a low dose of propofol reduces the intensity of pain at the site of injection compared with no occlusion. METHODS Bilateral 0.5-ml injections of an emulsion containing 10 mg/ml of propofol were given over 30 s in 75 adult surgical patients. Each patient was given one injection with and one without 60-s occlusion of the cannulated vein with a 10-min interval, and asked to score the maximal pain intensity on a visual analogue scale (VAS). RESULTS The maximal pain intensity [median (25th percentile; 75th percentile), range] at the site of injection was 0.5 (0; 3.5), 0-8.0 VAS units with venous occlusion and 0.5 (0; 1.4), 0-6.0 VAS units without occlusion (P= 0.042). Pain was first reported within 20 s regardless of the study regimen and was not prolonged by local venous occlusion. CONCLUSION Venous occlusion augments pain intensity at the site of propofol injection without prolonging pain, implying that propofol-induced pain is determined more by the blood concentration than by the duration of intravascular exposure. The low intensity of pain induced by low-dose propofol and the fading of pain despite sustained exposure suggest that initial low-dose administration of propofol should be evaluated for the attenuation of local pain induced by higher intravenous doses of propofol.
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Affiliation(s)
- E Liljeroth
- Department of Anaesthesiology and Intensive Care Medicine, Karolinska Institute, Karolinska University Hospital Solna, Stockholm, Sweden
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Ihmsen H, Jeleazcov C, Schüttler J, Schwilden H, Bremer F. [Pharmacodynamics of two different propofol formulations]. Anaesthesist 2006; 55:635-42. [PMID: 16479409 DOI: 10.1007/s00101-006-0987-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
BACKGROUND Propofol is nowadays available in various lipid formulations. We compared two different propofol formulations with respect to pharmacodynamics, using the EEG and clinical signs. MATERIALS AND METHODS Ten volunteers received Diprivan 1% and Propofol 1% MCT Fresenius as a computer controlled infusion with increasing propofol target concentrations. A sigmoid E(max) model with effect compartment was estimated for the median frequency of the EEG power spectrum, based on measured arterial propofol plasma concentrations. Clinical pharmacodynamics were assessed by reaction on acoustic stimuli, eyelid reflex and corneal reflex. RESULTS The drugs did not differ in pharmacodynamics with respect to EEG (EC(50) 2.1+/-0.6 for Diprivan and 2.1+/-0.5 microg/ml for Propofol Fresenius) and clinical signs. The pharmacodynamic model was characterized by a steep concentration effect relationship and a distinct hysteresis between propofol plasma concentration and effect (k(e0) 0.12+/-0.04 and 0.12+/-0.5 min(-1)). CONCLUSIONS The investigated lipid formulations have no influence on the pharmacodynamics of propofol.
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Affiliation(s)
- H Ihmsen
- Anästhesiologische Klinik, Friedrich-Alexander-Universität Erlangen-Nürnberg, Krankenhausstrasse 12, 91054 Erlangen.
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Bachmann-Mennenga B, Ohlmer A, Boedeker RH, Mann M, Mühlenbruch B, Heesen M. Preventing pain during injection of propofol: effects of a new emulsion with lidocaine addition. Eur J Anaesthesiol 2006; 24:33-8. [PMID: 16824248 DOI: 10.1017/s0265021506000974] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/16/2006] [Indexed: 11/07/2022]
Abstract
BACKGROUND AND OBJECTIVE Previous studies found that lidocaine addition to propofol long-chain triglyceride was associated with a lower incidence of injection pain than medium-chain triglyceride/long-chain triglyceride formulation, but the incidence was still high (31-40%). Our study investigated whether the incidence of injection pain could be further reduced by the addition of lidocaine (10 mg, 20:1) to propofol medium-chain triglyceride/long-chain triglyceride. METHODS In a randomized double-blind controlled trial 464 patients scheduled to undergo regional anaesthesia were assigned to receive one of the following four options: propofol medium-chain triglyceride/long-chain triglyceride + lidocaine, propofol long-chain triglyceride + lidocaine, propofol medium-chain triglyceride/long-chain triglyceride or propofol long-chain triglyceride. Propofol was injected to reach grade 3 of the Observer's Assessment of Alertness/Sedation scale. RESULTS Incidence of injection pain was 18% in the propofol medium-chain triglyceride/long-chain triglyceride + lidocaine group, 31% in the propofol long-chain triglyceride + lidocaine group, 47% in the propofol medium-chain triglyceride/long-chain triglyceride group and 60% in the long-chain triglyceride group. Propofol medium-chain triglyceride/long-chain triglyceride + lidocaine was associated with a statistically significant reduced incidence of injection pain compared with propofol long-chain triglyceride +lidocaine (P =0.0249, number needed to treat =7.7). CONCLUSIONS Premixing propofol medium-chain triglyceride/long-chain triglyceride with lidocaine is one of the most effective measures currently available to reduce the incidence of injection pain in sedated patients during regional anaesthesia.
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Suzuki H, Miyazaki H, Andoh T, Yamada Y. Propofol formulated with long-/medium-chain triglycerides reduces the pain of injection by target controlled infusion. Acta Anaesthesiol Scand 2006; 50:568-71. [PMID: 16643226 DOI: 10.1111/j.1399-6576.2006.00986.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Propofol is a widely used intravenous anesthetic although its injection pain is a common and unpleasant problem. Long-/medium-chain triglyceride (LCT/MCT) propofol has been introduced, as its low free propofol content is expected to reduce injection pain compared with LCT propofol. Target controlled infusion (TCI) differs from conventional induction in the initial infusion pattern. During induction using TCI, we investigated injection pain caused by two propofol solutions with different triglyceride compositions. METHODS Fifty patients, ASA I-II, with adequate communicative ability, were randomly assigned to two groups. TCI was conducted with Diprifusor for LCT and with BeComSim (custom-made software) for LCT/MCT. The target blood concentration was set at 4 microg/ml for both groups. At 30, 60, and 120 s after the infusion, patients were asked questions regarding the severity of pain on a 0-10 pain score. The total dose of propofol and the time required to induce anesthesia were also investigated. RESULTS The LCT/MCT propofol group had a larger number of pain-free patients and showed lower severity of pain than the LCT group [the number of pain-free patients being 11 and 3, respectively (P < 0.05), and median maximum pain being 0 and 4.5, respectively (P < 0.01)]. The dose and time required for induction were not significantly different between the groups (dose of 84 +/- 27 and 80 +/- 24 mg, respectively, and time of 119 +/- 60 and 107 +/- 55 s, respectively). CONCLUSION Our study showed that the frequency and severity of pain during TCI induction with propofol could be significantly reduced using LCT/MCT propofol rather than LCT propofol.
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Affiliation(s)
- H Suzuki
- Department of Anaesthesiology, Saiseikai Yokohamashi Nanbu Hospital, Kanagawa, Japan
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Gutmann A, Pessenbacher K, Gschanes A, Eggenreich U, Wargenau M, Toller W. Propofol anesthesia in spontaneously breathing children undergoing magnetic resonance imaging: comparison of two propofol emulsions. Paediatr Anaesth 2006; 16:266-74. [PMID: 16490090 DOI: 10.1111/j.1460-9592.2005.01777.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
BACKGROUND This study evaluated a propofol-based anesthesia regimen with spontaneous breathing in pediatric patients scheduled for magnetic resonance imaging (MRI). METHODS In this prospective, randomized, double-blind study propofol formulated with long-chain triglycerides (LCT) and mixed medium-chain/long-chain triglycerides (MCT/LCT) were used. Ninety patients aged 2.4 months to 7.3 years were premedicated with intravenous midazolam. Lidocaine was injected prior to propofol to reduce injection pain. Anesthesia was induced and maintained by propofol. Glycopyrronium bromide was administered for saliva reduction. Hemodynamics, blood oxygen saturation and endtidal capnography were continuously monitored. All patients received additional oxygen. The aggregated propofol dose for induction and maintenance of anesthesia was analyzed for therapeutic equivalence. Incidence of injection pain, laboratory safety values, vital signs, and the adverse event profile were analyzed to compare tolerability and safety. RESULTS Propofol anesthesia was safe and successful in all children. Both propofol formulations were equivalent regarding dose requirements (mean induction and maintenance doses for anesthesia 2.0-4.0 mg.kg(-1) and 6.0-8.8 mg.kg(-1).h(-1) respectively; aggregated doses 8-13.26 mg.kg(-1)). There were no differences in drug safety such as hemodynamics, spontaneous breathing, injection pain, and laboratory values. Duration of induction and of recovery from anesthesia were short and all examinations were completed with minimal interruption. CONCLUSIONS Propofol-based short-term anesthesia was well suited for anesthesia during MRI procedures in the studied pediatric patients. There were no clinically relevant differences between the two propofol formulations.
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Affiliation(s)
- Anton Gutmann
- Department of Anaesthesiology and Intensive Care Medicine, Medical University Graz, Graz, Austria.
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Chen H, Zhang Z, Almarsson O, Marier JF, Berkovitz D, Gardner CR. A novel, lipid-free nanodispersion formulation of propofol and its characterization. Pharm Res 2005; 22:356-61. [PMID: 15835740 DOI: 10.1007/s11095-004-1872-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
PURPOSE Propofol is a widely used anesthetic agent with highly desirable fast "on" and "off" effects. It is currently formulated as lipid emulsions, which are known to support microbial growth. In this study, a novel, lipid-free nanodispersion formulation of propofol was characterized. METHODS The formulation was evaluated for its physical and chemical stability, in vitro compatibility with red blood cells, and its antimicrobial effectiveness. In vivo pharmacokinetic and pharmacodynamic properties of the formulation were evaluated in rats. RESULTS Our data suggest that this lipid-free formulation is physically and chemically stable. Compared to the commercial emulsion formulation Diprivan, it causes less hemolysis with red blood cells and has improved antimicrobial activity. In addition, the lipid-free formulation demonstrates similar pharmacological effects to Diprivan in rats. CONCLUSIONS This novel, lipid-free formulation exhibits improved in vitro properties without compromising in vivo effects, therefore representing a promising new alternative for propofol.
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Affiliation(s)
- Hongming Chen
- TransForm Pharmaceuticals, Inc., 29 Hartwell Avenue, Lexington, Massachusetts 02421, USA.
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20
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Abstract
BACKGROUND Local pain at the site of intravenous (iv) injection of propofol remains a considerable problem in clinical anaesthesiology, and particularly so in infants. The aim of the present study was to compare the influence of two different emulsions of propofol on local pain following iv administration. METHODS Eighty adult patients (ASA I-II) scheduled for ear-nose-throat or plastic surgery were randomly allocated into two study groups: A and B. A 1.0-mm teflon cannula (BD, Helsingborg, Sweden) was inserted into a dorsal vein on each hand. Each patient was given two 3.0-ml iv bolus injections of two different propofol emulsions of 10 mg ml(-1) over 2 s, one in each cannula, at 5-min intervals. The first study drug administered was Diprivan (AstraZeneca, Södertälie, Sweden) in group A (n = 34) and Propofol-Lipuro (Braun, Melsungen, Germany) in group B (n = 39). Each patient was then asked by a blinded investigator to score maximal pain intensity on a visual analogue scale (VAS). RESULTS The maximal intensity of propofol-induced local pain was significantly (P < 0.0001) lower after Propofol-Lipuro than after Diprivan--median 1 (25th percentile: 0; 75th percentile: 2) range 0-6 vs. 3 (0; 5) 0-9 VAS units. CONCLUSION The considerably lower intensity of local pain found to be associated with iv administration of the new drug formula Propofol-Lipuro indicates that emulsions of propofol based on medium- and long-chain triglycerides have a clinical advantage over traditional ones for induction of anaesthesia.
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Affiliation(s)
- E Liljeroth
- Department of Anaesthesia and Intensive Care, Karolinska University Hospital Solna, Stockholm, Sweden.
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Kam E, Abdul-Latif MS, McCluskey A. Comparison of Propofol-Lipuro with propofol mixed with lidocaine 10 mg on propofol injection pain. Anaesthesia 2004; 59:1167-9. [PMID: 15549974 DOI: 10.1111/j.1365-2044.2004.03964.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
A common drawback of propofol is pain on injection and lidocaine is commonly mixed with propofol to reduce its incidence and severity. We conducted a randomised, prospective, double-blind study to compare injection pain following the administration of two different formulations of propofol in 200 unpremedicated ASA I-III adult patients scheduled for elective surgery under general anaesthesia. Patients were allocated randomly into two groups to receive either Propofol-Lipuro without added lidocaine or Diprivan mixed with lidocaine 10 mg. Five ml of the study solution was injected at a constant rate over 15 s and patients graded any associated pain or discomfort using a four-point verbal rating scale. The incidence of propofol injection pain was virtually identical in both study groups with 37/98 (38%) patients experiencing pain or discomfort following Propofol-Lipuro compared with 35/98 (36%) after Diprivan (p = 0.88). We observed no significant difference in pain scores between the groups (p = 0.67). Moderate or severe injection pain was experienced by 12/98 (12%) patients given Propofol-Lipuro compared with 8/98 (8%) given Diprivan (p = 0.48).
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Affiliation(s)
- E Kam
- Department of Anaesthesia, Stepping Hill Hospital, Stockport, SK2 7JE, UK
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Adam S, van Bommel J, Pelka M, Dirckx M, Jonsson D, Klein J. Propofol-Induced Injection Pain: Comparison of a Modified Propofol Emulsion to Standard Propofol with Premixed Lidocaine. Anesth Analg 2004; 99:1076-1079. [PMID: 15385353 DOI: 10.1213/01.ane.0000130344.17898.cd] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Propofol is well known for its association with pain on injection. The most frequently used method to reduce this pain is premixture with lidocaine. Recently, a modified lipid emulsion of propofol containing medium-chain triglycerides (MCT) with long-chain triglycerides (LCT), in contrast to the usual LCT formulation, has been advocated to alleviate pain. In a randomized, prospective, controlled, double-blind study on 222 surgical patients, we compared the effect of the two solutions on the incidence and intensity of injection pain. Patients were randomly allocated to receive either propofol MCT/LCT (group M; n = 109) or standard propofol LCT with the addition of 20 mg of lidocaine (2 mL of lidocaine 1%) to 200 mg of propofol (group L; n = 113). Pain scores were assessed using a verbal analog scale (VAS) ranging from 0-10. Group L was found to have significantly less pain on the injection of propofol (mean VAS, 2.5 +/- 2.9) (mean +/- sd) than group M (mean VAS, 3.8 +/- 3.2; P = 0.002). Regarding postoperative recall of pain on injection, patients in group L indicated significantly less pain (mean VAS, 2.2 +/- 2.4) than patients in group M (mean VAS, 3.0 +/- 2.7; P = 0.02). Premixing of 20 mg of lidocaine (2 mL of lidocaine 1%) to 200 mg of standard propofol LCT causes less pain on injection than propofol MCT/LCT and thus increases patient comfort.
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Affiliation(s)
- Sigrid Adam
- Department of Anesthesiology, Erasmus Medical Center Rotterdam, The Netherlands
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Calvo R, Telletxea S, Leal N, Aguilera L, Suarez E, De La Fuente L, Martin-Suarez A, Lukas JC. Influence of formulation on propofol pharmacokinetics and pharmacodynamics in anesthetized patients. Acta Anaesthesiol Scand 2004; 48:1038-48. [PMID: 15315624 DOI: 10.1111/j.0001-5172.2004.00467.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND In anesthesia with propofol, variability persists besides sophisticated effect targeting. Drug formulation may be another factor. We have analyzed, retrospectively, the pharmacokinetics (PK) and pharmacodynamics (PD) in monitored surgery patients anesthetized with one each of five formulations of propofol. METHODS Propofol 1% ('form' 1: Diprivan(Zeneca Limited, Macclesfield, UK), 2: Recofol(Schering Espana, Madrid, Spain), 3: Ivofol(Juste, Madrid, Spain), 4: Propofol Abbott (Abbott Laboratories, Madrid, Spain), 5: Fresenius (Fresenius Kabi Espana, Barcelona, Spain)) was administered to 77 ASA I-II patients of age [mean (range) 44 (18-65) years]. Induction of anesthesia was with varying propofol doses up to endpoints of either 60 on the Bispectral Index system (BIS) in group I (n = 48, model development) or standard clinical signs in group II (n = 29, validation). Maintenance was with three 10-min infusions of 10, 8 and 6 mg kg(-1) h(-1). Three blood samples were obtained from each subject, immediately after induction, and at 15 and 30 min on maintenance, with BIS and hemodynamic variables recorded at these times also. Total and free blood concentrations (Cb) of propofol were determined with HPLC. Pharmacokinetic and PD models with link equilibration rate ke0, were studied with a mixed-effects procedure (NONMEM). RESULTS The induction dose (group I) showed large interindividual variability [mean (range) 163 (90-290 mg)] that correlated significantly with age, basal systolic blood pressure and formulation. The PK of propofol (basic model) was described by a one-compartment model with (typical value [interindividual coefficient of variation percent (CV%)]) CL=2.30 l min(-1) (27%) and V=8.40 l (80%). Weight (WT) and formulation, within NONMEM, were found to be significant covariates for CL and V, reducing their CV% to 25% and 74%, respectively. The final PK/PD model, which includes formulation, showed a 50% reduction in the CV% for both the ke0 and the residual error. This PK/PD model was validated in group II with 33% precision and no bias. CONCLUSION The PK and PD are not equal for all formulations, which contributes to an increase in variability of the observed effect.
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Affiliation(s)
- R Calvo
- Department of Pharmacology, Faculty of Medicine, University of the Basque Country, Leioa, Vizcaya, Spain.
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Abstract
OBJECTIVE To assess the effect of granisetron pretreatment in alleviating propofol injection pain. STUDY DESIGN A randomized, controlled, double-blind study, using venous retention with a tourniquet. MATERIALS AND METHODS One hundred fifty adult patients were randomly assigned to one of three groups: group 1 (who received 5 mL of 0.9% saline pretreatment), group 2 (who received 5 mL lidocaine [40 mg in 0.9% saline] pretreatment), and group 3 (who received 5 mL granisetron [2 mg in 0.9% saline] pretreatment). Injections were given in the largest vein on the dorsum of the hand. After 2 minutes, the tourniquet was released and one fourth of the total calculated dose of propofol (2.5 mg/kg body weight) was administered and pain assessment was made. RESULTS Lidocaine and granisetron significantly reduced the incidence and severity of propofol injection pain more than placebo (P < 0.001). The efficacy of granisetron in alleviating the pain on injection of propofol was no different from lidocaine. CONCLUSIONS Granisetron pretreatment may be used to reduce the incidence of pain on injection of propofol, an advantage added to the useful prevention of postoperative nausea and vomiting.
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Affiliation(s)
- Prakash K Dubey
- Department of Anesthesiology, Indira Gandhi Institute of Medical Sciences, Patna 800 013, India
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Krasowski MD, Hong X, Hopfinger AJ, Harrison NL. 4D-QSAR analysis of a set of propofol analogues: mapping binding sites for an anesthetic phenol on the GABA(A) receptor. J Med Chem 2002; 45:3210-21. [PMID: 12109905 PMCID: PMC2864546 DOI: 10.1021/jm010461a] [Citation(s) in RCA: 69] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
A training set of 27 propofol (2,6-diisopropylphenol) analogues was used to construct four-dimensional (4D) quantitative structure-activity relationship (QSAR) models for three screens of biological activity: loss of righting reflex (LORR) in tadpoles, enhancement of agonist activity at the gamma-aminobutyric acid type A (GABA(A)) receptor, and direct (agonist-independent) activation of the receptor. The three resulting 4D-QSAR models are almost identical in form, and all suggest three key ligand-receptor interaction sites. The formation of an intermolecular hydrogen bond involving the proton of the ligand -OH group is the most important binding interaction. A hydrophobic pocket binding interaction involving the six-substituent is the second most significant binding site, and a similar hydrophobic pocket binding interaction near the two-substituent is the third postulated binding site from the 4D-QSAR models. A test set of eight compounds was used to evaluate the tadpole LORR 4D-QSAR model. Those compounds highly congeneric to the training set compounds were accurately predicted. However, compounds exploring substituent sites and/or electronic structures different from the training set were less well-predicted. Overall, the results show a striking similarity between the models of the sites responsible for anesthesia and those mediating effects of the training set of propofol analogues on the GABA(A) receptor; it follows that the GABA(A) receptor is therefore the likely site of propofol's anesthetic action.
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Affiliation(s)
- Matthew D Krasowski
- Department of Anesthesia and Critical Care, University of Chicago Medical Center, 5841 South Maryland Avenue, Chicago, IL 60637, USA
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Knibbe CA, Voortman HJ, Aarts LP, Kuks PF, Lange R, Langemeijer HJ, Danhof M. Pharmacokinetics, induction of anaesthesia and safety characteristics of propofol 6% SAZN vs propofol 1% SAZN and Diprivan-10 after bolus injection. Br J Clin Pharmacol 1999; 47:653-60. [PMID: 10383543 PMCID: PMC2014258 DOI: 10.1046/j.1365-2125.1999.00942.x] [Citation(s) in RCA: 22] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
AIMS In order to avoid the potential for elevated serum lipid levels as a consequence of long term sedation with propofol, a formulation of propofol 6% in Lipofundin(R) MCT/LCT 10% (Propofol 6% SAZN) has been developed. The pharmacokinetics, induction of anaesthesia and safety characteristics of this new formulation were investigated after bolus injection and were compared with the commercially available product (propofol 1% in Intralipid(R) 10%, Diprivan-10) and propofol 1% in Lipofundin(R) MCT/LCT 10% (Propofol 1% SAZN). METHODS In a randomised double-blind study, 24 unpremedicated female patients received an induction dose of propofol of 2.5 mg kg-1 over 60 s which was followed by standardized balanced anaesthesia. The patients were randomized to receive propofol as Propofol 6% SAZN, Propofol 1% SAZN or Diprivan-10. RESULTS For all formulations the pharmacokinetics were adequately described by a tri-exponential equation, as the propofol concentrations collected early after the injection suggested an additional initial more rapid phase. The average values for clearance (CL), volume of distribution at steady-state (Vd,ss ), elimination half-life (t1/2,z ) and distribution half-life (t1/2, lambda2) observed in the three groups were 32+/-1.5 ml kg-1 min-1, 2. 0+/-0.18 l kg-1, 95+/-5.6 min and 3.4+/-0.20 min, respectively (mean+/-s.e.mean, n=24) and no significant differences were noted between the three formulations (P >0.05). The half-life of the additional initial distribution phase (t1/2,lambda1 ) in all subjects ranged from 0.1 to 0.6 min. Anaesthesia was induced successfully and uneventfully in all cases, and the quality of induction was adequate in all 24 patients. The induction time did not vary between the three formulations and the average induction time observed in the three groups was 51+/-1.3 s which corresponded to an induction dose of propofol of 2.1+/-0.06 mg kg-1 (mean+/-s.e. mean, n=24). The percentage of patients reporting any pain on injection did not vary between the formulations and was 17% for the three groups. No postoperative phlebitis or other venous sequelae of the vein used for injection occurred in any of the patients at recovery of anaesthesia nor after 24 h. CONCLUSIONS From the above results, we conclude that the alteration of the type of emulsion and the higher concentration of propofol in the new parenteral formulation of propofol does not affect the pharmacokinetics and induction characteristics of propofol, compared with the currently available product. Propofol 6% SAZN can be administered safely and has the advantage of a reduction of the load of fat and emulsifier which may be preferable when long term administration of propofol is required.
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Affiliation(s)
- C A Knibbe
- Department of Clinical Pharmacy, St Antonius Hospital, P.O. Box 2500, 3430 EM Nieuwegein, The Netherlands
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Musser JB, Fontana JL, Mongan PD. The Anesthetic and Physiologic Effects of an Intravenous Administration of a Halothane Lipid Emulsion (5% vol/vol). Anesth Analg 1999. [DOI: 10.1213/00000539-199903000-00038] [Citation(s) in RCA: 22] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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