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Märtson AG, Barber KE, Crass RL, Hites M, Kloft C, Kuti JL, Nielsen EI, Pai MP, Zeitlinger M, Roberts JA, Tängdén T. The pharmacokinetics of antibiotics in patients with obesity: a systematic review and consensus guidelines for dose adjustments. THE LANCET. INFECTIOUS DISEASES 2025:S1473-3099(25)00155-0. [PMID: 40383125 DOI: 10.1016/s1473-3099(25)00155-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Revised: 02/14/2025] [Accepted: 02/25/2025] [Indexed: 05/20/2025]
Abstract
Obesity can cause physiological changes resulting in antibiotic pharmacokinetic alterations and suboptimal drug exposures. This systematic review aimed to summarise the available evidence on this topic and provide guidance for dose adjustment of antibiotics in adult (age ≥18 years) patients with obesity (BMI >30 kg/m2). We searched PubMed, Embase, and CENTRAL databases to find relevant studies published between database inception and Dec 30, 2023. We initially identified 6113 studies, which became 4654 studies after duplicate removal, and 128 studies were included in the final review. β-lactam antibiotics were most commonly studied (57 studies), followed by the group of glycopeptides, lipoglycopeptides, and oxazolidinones (45 studies). The certainty of evidence was low or very low for all antibiotics and a meta-analysis was not possible due to the heterogeneity of study populations and methods. Obesity modestly alters the pharmacokinetics of β-lactam antibiotics, but evidence does not support routine dose adjustments. For aminoglycosides and glycopeptides, the impact of obesity on pharmacokinetics is evident and weight-based dosing is recommended. Data are sparse for other antibiotic classes and research needs are described. In the absence of robust pharmacokinetic data, therapeutic drug monitoring can be used to guide individualised dosing.
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Affiliation(s)
- Anne-Grete Märtson
- Division of Systems Pharmacology and Pharmacy, Leiden Academic Centre for Drug Research, Leiden University, Leiden, Netherlands
| | - Katie E Barber
- School of Pharmacy, University of Mississippi, Jackson, MS, USA
| | - Ryan L Crass
- A2-Ai, Ann Arbor, MI, USA; College of Pharmacy, University of Michigan, Ann Arbor, MI, USA
| | - Maya Hites
- Clinic of Infectious Diseases, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Brussels, Belgium
| | - Charlotte Kloft
- Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Berlin, Germany
| | - Joseph L Kuti
- Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA
| | | | - Manjunath P Pai
- Department of Clinical Pharmacy, University of Michigan, Ann Arbor, MI, USA
| | - Markus Zeitlinger
- Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
| | - Jason A Roberts
- University of Queensland Centre for Clinical Research, Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia; Herston Infectious Diseases Institute, Metro North Health, Brisbane, QLD, Australia; Department of Pharmacy and Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia; UR UM 103, University of Montpellier, Division of Anesthesia Critical Care and Emergency and Pain Medicine, Nimes University Hospital, Nimes, France
| | - Thomas Tängdén
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
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Dickerson RN, Andromalos L, Brown JC, Correia MITD, Pritts W, Ridley EJ, Robinson KN, Rosenthal MD, van Zanten ARH. Obesity and critical care nutrition: current practice gaps and directions for future research. Crit Care 2022; 26:283. [PMID: 36127715 PMCID: PMC9486775 DOI: 10.1186/s13054-022-04148-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Accepted: 08/25/2022] [Indexed: 11/25/2022] Open
Abstract
Background This review has been developed following a panel discussion with an international group of experts in the care of patients with obesity in the critical care setting and focuses on current best practices in malnutrition screening and assessment, estimation of energy needs for patients with obesity, the risks and management of sarcopenic obesity, the value of tailored nutrition recommendations, and the emerging role of immunonutrition. Patients admitted to the intensive care unit (ICU) increasingly present with overweight and obesity that require individualized nutrition considerations due to underlying comorbidities, immunological factors such as inflammation, and changes in energy expenditure and other aspects of metabolism. While research continues to accumulate, important knowledge gaps persist in recognizing and managing the complex nutritional needs in ICU patients with obesity. Available malnutrition screening and assessment tools are limited in patients with obesity due to a lack of validation and heterogeneous factors impacting nutrition status in this population. Estimations of energy and protein demands are also complex in patients with obesity and may include estimations based upon ideal, actual, or adjusted body weight. Evidence is still sparse on the role of immunonutrition in patients with obesity, but the presence of inflammation that impacts immune function may suggest a role for these nutrients in hemodynamically stable ICU patients. Educational efforts are needed for all clinicians who care for complex cases of critically ill patients with obesity, with a focus on strategies for optimal nutrition and the consideration of issues such as weight stigma and bias impacting the delivery of care. Conclusions Current nutritional strategies for these patients should be undertaken with a focus on individualized care that considers the whole person, including the possibility of preexisting comorbidities, altered metabolism, and chronic stigma, which may impact the provision of nutritional care. Additional research should focus on the applicability of current guidelines and evidence for nutrition therapy in populations with obesity, especially in the setting of critical illness.
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Wong S, Reuter SE, Jones GR, Stocker SL. Review and evaluation of vancomycin dosing guidelines for obese individuals. Expert Opin Drug Metab Toxicol 2022; 18:323-335. [PMID: 35815356 DOI: 10.1080/17425255.2022.2098106] [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: 11/04/2022]
Abstract
INTRODUCTION Vancomycin dosing decisions are informed by factors such as body weight and renal function. It is important to understand the impact of obesity on vancomycin pharmacokinetics and how this may influence dosing decisions. Vancomycin dosing guidelines use varied descriptors of body weight and renal function. There is uncertainty whether current dosing guidelines result in attainment of therapeutic targets in obese individuals. AREAS COVERED Literature was explored using PubMed, Embase and Google Scholar for articles from January 1980 to July 2021 regarding obesity-driven physiological changes, their influence on vancomycin pharmacokinetics and body size descriptors and renal function calculations in vancomycin dosing. Pharmacokinetic simulations reflective of international vancomycin dosing guidelines were conducted to evaluate the ability of using total, ideal and adjusted body weight, as well as Cockcroft-Gault and CKD-EPI equations to attain an area-under-the-curve to minimum inhibitory concentration ratio (AUC24/MIC) target (400-650) in obese individuals. EXPERT OPINION Vancomycin pharmacokinetics in obese individuals remains debated. Guidelines that determine loading doses using total body weight, and maintenance doses adjusted based on renal function and adjusted body weight, may be most appropriate for obese individuals. Use of ideal body weight leads to subtherapeutic vancomycin exposure and underestimation of renal function.
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Affiliation(s)
- Sherilyn Wong
- UniSA Clinical and Health Sciences, University of South Australia, Adelaide, Australia
| | - Stephanie E Reuter
- UniSA Clinical and Health Sciences, University of South Australia, Adelaide, Australia
| | - Graham Rd Jones
- St Vincent's Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, Australia.,Department of Chemical Pathology and Clinical Pharmacology, SydPath, St Vincent's Hospital, Darlinghurst, Australia
| | - Sophie L Stocker
- St Vincent's Clinical School, Faculty of Medicine, The University of New South Wales, Sydney, Australia.,Sydney School of Pharmacy, The University of Sydney, Sydney, Australia.,Department of Clinical Pharmacology & Toxicology, St Vincent's Hospital Sydney, Darlinghurst, Australia
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Xu KY, Li D, Hu ZJ, Zhao CC, Bai J, Du WL. Vancomycin dosing in an obese patient with acute renal failure: A case report and review of literature. World J Clin Cases 2022; 10:6218-6226. [PMID: 35949852 PMCID: PMC9254177 DOI: 10.12998/wjcc.v10.i18.6218] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 01/19/2022] [Accepted: 04/22/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Vancomycin is the most commonly used drug for methicillin-resistant Staphylococcus aureus. The empirical clinical doses of vancomycin based on non-obese patients may not be optimal for obese ones.
CASE SUMMARY This study reports a case of vancomycin dosing adjustment in an obese patient (body mass index 78.4 kg/m2) with necrotizing fasciitis of the scrotum and left lower extremity accompanied with acute renal failure. Dosing adjustment was performed based on literature review and factors that influence pharmacokinetic parameters are analyzed. The results of the blood drug concentration monitoring confirmed the successful application of our dosing adjustment strategy in this obese patient. Total body weight is an important consideration for vancomycin administration in obese patients, which affects the volume of distribution and clearance of vancomycin. The alterations of pharmacokinetic parameters dictate that vancomycin should be dose-adjusted when applied to obese patients. At the same time, the pathophysiological status of patients, such as renal function, which also affects the dose adjustment of the patient, should be considered.
CONCLUSION Monitoring vancomycin blood levels in obese patients is critical to help adjust the dosing regimen to ensure that vancomycin concentrations are within the effective therapeutic range and to reduce the incidence of renal injury.
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Affiliation(s)
- Kun-Yan Xu
- Department of Pharmacy, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
| | - Dan Li
- Department of Pharmacy, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
| | - Zhen-Jie Hu
- Department of Intensive Care Unit, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
| | - Cong-Cong Zhao
- Department of Intensive Care Unit, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
| | - Jing Bai
- Department of Pharmacy, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
| | - Wen-Li Du
- Department of Pharmacy, Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
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Pediatric obesity and perioperative medicine. Curr Opin Anaesthesiol 2021; 34:299-305. [PMID: 33935177 DOI: 10.1097/aco.0000000000000991] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW Childhood obesity is a public health emergency that has reached a pandemic level and imposed a massive economic burden on healthcare systems. Our objective was to provide an update on (1) challenges of obesity definition and classification in the perioperative setting, (2) challenges of perioperative patient positioning and vascular access, (3) perioperative implications of childhood obesity, (3) anesthetic medication dosing and opioid-sparing techniques in obese children, and (4) research gaps in perioperative childhood obesity research including a call to action. RECENT FINDINGS Despite the near axiomatic observation that obesity is a pervasive clinical problem with considerable impact on perioperative health, there have only been a handful of research into the many ramifications of childhood obesity in the perioperative setting. A nuanced understanding of the surgical and anesthetic risks associated with obesity is essential to inform patients' perioperative consultation and their parents' counseling, improve preoperative risk mitigation, and improve patients' rescue process when complications occur. SUMMARY Anesthesiologists and surgeons will continue to be confronted with an unprecedented number of obese or overweight children with a high risk of perioperative complications.
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Tapking C, Houschyar KS, Rontoyanni VG, Hundeshagen G, Kowalewski KF, Hirche C, Popp D, Wolf SE, Herndon DN, Branski LK. The Influence of Obesity on Treatment and Outcome of Severely Burned Patients. J Burn Care Res 2020; 40:996-1008. [PMID: 31294797 DOI: 10.1093/jbcr/irz115] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Obesity and the related medical, social, and economic impacts are relevant multifactorial and chronic conditions that also have a meaningful impact on outcomes following a severe injury, including burns. In addition to burn-specific difficulties, such as adequate hypermetabolic response, fluid resuscitation, and early wound coverage, obese patients also present with common comorbidities, such as arterial hypertension, diabetes mellitus, or nonalcoholic fatty liver disease. In addition, the pathophysiologic response to severe burns can be enhanced. Besides the increased morbidity and mortality compared to burn patients with normal weight, obese patients present a challenge in fluid resuscitation, perioperative management, and difficulties in wound healing. The present work is an in-depth review of the current understanding of the influence of obesity on the management and outcome of severe burns.
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Affiliation(s)
- Christian Tapking
- Department of Surgery, University of Texas Medical Branch, Galveston.,Shriners Hospitals for Children, Galveston, Texas.,Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Germany
| | - Khosrow S Houschyar
- Department of Plastic Surgery, Hand Surgery, Sarcoma Center, BG University Hospital, Ruhr University, Bochum, Germany
| | - Victoria G Rontoyanni
- Department of Surgery, University of Texas Medical Branch, Galveston.,Metabolism Unit, Shriners Hospitals for Children, Galveston, Texas
| | - Gabriel Hundeshagen
- Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Germany
| | | | - Christoph Hirche
- Department of Hand, Plastic and Reconstructive Surgery, Burn Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Germany
| | - Daniel Popp
- Department of Surgery, University of Texas Medical Branch, Galveston.,Shriners Hospitals for Children, Galveston, Texas.,Department of Urology, University Medical Center Mannheim, University of Heidelberg, Germany
| | - Steven E Wolf
- Department of Surgery, University of Texas Medical Branch, Galveston.,Shriners Hospitals for Children, Galveston, Texas
| | - David N Herndon
- Department of Surgery, University of Texas Medical Branch, Galveston
| | - Ludwik K Branski
- Department of Surgery, University of Texas Medical Branch, Galveston.,Shriners Hospitals for Children, Galveston, Texas.,Division of Plastic, Aesthetic and Reconstructive Surgery, Department of Surgery, Medical University of Graz, Austria
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Phoon PHY, Hwang NC. Deep Sternal Wound Infection: Diagnosis, Treatment and Prevention. J Cardiothorac Vasc Anesth 2020; 34:1602-1613. [DOI: 10.1053/j.jvca.2019.09.019] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Revised: 08/28/2019] [Accepted: 09/12/2019] [Indexed: 12/18/2022]
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Sridharan K, Al Daylami A, Ajjawi R, Al-Ajooz H, Veeramuthu S. Clinical Pharmacokinetics of Vancomycin in Critically Ill Children. Eur J Drug Metab Pharmacokinet 2020; 44:807-816. [PMID: 31301023 DOI: 10.1007/s13318-019-00568-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
BACKGROUND AND OBJECTIVE Critically ill children exhibit altered pharmacokinetic parameters of vancomycin, mainly due to altered renal excretion and volume of distribution (as a result of altered plasma protein concentrations). We assessed the pharmacokinetic parameters of vancomycin in this subpopulation. METHODS Vancomycin trough concentrations in critically ill children were obtained following first dose and at steady state. Using a one-compartment model, clearance (CL), volume of distribution (Vd), elimination half-life (t1/2), and area under the time-concentration curve for 24 h (AUC0-24) were estimated. Subgroup analyses were carried out, with patients differentiated based on age, renal clearance, outcome, and renal dysfunction. Protein-free vancomycin concentrations were calculated using a previously reported formula. RESULTS Twenty-two samples were evaluated for first-dose and 182 for steady-state pharmacokinetics, and similar pharmacokinetic parameter values were observed at first dose and at steady state. Only 36.4% and 47.3% of the samples attained the recommended AUC0-24 (mg·hr/L) of > 400 at first dose and at steady state, while 62.5% of the patients with renal dysfunction achieved this target. Nearly 40% of the patients had augmented renal clearance (ARC), which was associated with higher CL, shorter t1/2, and lower AUC values. Amongst the patients with ARC, none had AUC0-24 (mg·hr/L) > 400 at first dose, while 16% achieved this target at steady state. Volume of distribution was significantly higher in infants and a decreasing trend was observed in toddlers, children, and older children at steady state. Children with renal dysfunction had lower CL, prolonged t1/2, and higher AUC values than patients with normal renal clearance at first dose. A good correlation was observed between trough concentration and AUC0-24, as corroborated by the area under the receiver operating characteristic curve. The median fraction of protein-free vancomycin was around 77%. CONCLUSION Vancomycin dosing strategies in younger children should be revisited, and increased doses should be considered for critically ill children with ARC in order to achieve therapeutic concentrations of AUC0-24.
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Affiliation(s)
- Kannan Sridharan
- Department of Pharmacology and Therapeutics, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain.
| | - Amal Al Daylami
- Department of Pediatrics, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain.,Pediatric Intensive Care Unit, Salmaniya Medical Complex, Ministry of Health, Manama, Bahrain
| | - Reema Ajjawi
- Pediatric Intensive Care Unit, Salmaniya Medical Complex, Ministry of Health, Manama, Bahrain
| | - Husain Al-Ajooz
- Pediatric Intensive Care Unit, Salmaniya Medical Complex, Ministry of Health, Manama, Bahrain
| | - Sindhan Veeramuthu
- Department of Pharmacology and Therapeutics, College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain
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Masich AM, Kalaria SN, Gonzales JP, Heil EL, Tata AL, Claeys KC, Patel D, Gopalakrishnan M. Vancomycin Pharmacokinetics in Obese Patients with Sepsis or Septic Shock. Pharmacotherapy 2020; 40:211-220. [PMID: 31957057 DOI: 10.1002/phar.2367] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
STUDY OBJECTIVES Obese patients with sepsis or septic shock may have altered vancomycin pharmacokinetics compared with the general population that may result in improper dosing or inadequate drug concentrations. The objective of this study was to characterize vancomycin pharmacokinetics in obese patients with sepsis or septic shock, and to develop a novel pharmacokinetic dosing model based on pharmacokinetic-pharmacodynamic target requirements. DESIGN Prospective observational pharmacokinetic study. SETTING Large quaternary academic medical center. PATIENTS Sixteen obese (body mass index [BMI] 30 kg/m2 or higher) adults with sepsis and either a gram-positive bacteremia or requiring vasopressor support (septic shock), who were receiving vancomycin between November 2016 and June 2018, were included. Patients were excluded if they were receiving renal replacement therapy or extracorporeal membrane oxygenation, treatment for central nervous system infections, pregnant, or receiving vancomycin for surgical prophylaxis. INTERVENTION Four blood samples per patient were collected following a single dose of vancomycin: one peak serum vancomycin level (within 1-2 hrs of infusion completion), two random levels during the dosing interval, and one trough level (within 30-60 min of the next dose) were measured. MEASUREMENTS AND MAIN RESULTS A population pharmacokinetic model was developed to describe vancomycin concentrations over time. Simulations to determine optimal dosing were performed using the pharmacokinetic model with different ranges of creatinine clearance (Clcr ) and different vancomycin daily doses. Median age of the patients was 62 years; median BMI was 36.1 kg/m2 , Acute Physiology and Chronic Health Evaluation II score was 26, and Sequential Organ Failure Assessment score was 11. Eleven patients (69%) had an acute kidney injury. Median initial vancomycin dose was 15 mg/kg; median vancomycin trough concentration was 17 mg/L. A one-compartment model best characterized the pharmacokinetics of vancomycin in obese patients with sepsis or septic shock. Volume of distribution was slightly increased in this population (0.8 L/kg) compared with the general population (0.7 L/kg). Only Clcr effect on drug clearance was found to be significant (decrease in the objective function value by 16.4 points), confirming that it is a strong predictor of vancomycin clearance. CONCLUSION To our knowledge, this study provides the first population-based pharmacokinetic model in obese patients with sepsis or septic shock. The nomograms generated from this pharmacokinetic model provide a simplified approach to vancomycin dosing in this patient population.
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Affiliation(s)
- Anne M Masich
- Department of Pharmacy, Virginia Commonwealth University Health System, Richmond, Virginia
| | - Shamir N Kalaria
- Center for Translational Medicine, University of Maryland School of Pharmacy, Baltimore, Maryland
| | | | - Emily L Heil
- Department of Pharmacy Practice and Science, University of Maryland School of Pharmacy, Baltimore, Maryland
| | - Asha L Tata
- Department of Pharmacy, University of Maryland Medical Center, Baltimore, Maryland
| | - Kimberly C Claeys
- Department of Pharmacy Practice and Science, University of Maryland School of Pharmacy, Baltimore, Maryland
| | - Devang Patel
- Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland
| | - Mathangi Gopalakrishnan
- Center for Translational Medicine, University of Maryland School of Pharmacy, Baltimore, Maryland
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Chu C, Lteif L, Young N. The Daniel K. Inouye College of Pharmacy Scripts: Obesity: The Drug Dose Debate. HAWAI'I JOURNAL OF MEDICINE & PUBLIC HEALTH : A JOURNAL OF ASIA PACIFIC MEDICINE & PUBLIC HEALTH 2017; 76:162-165. [PMID: 28607835 PMCID: PMC5458583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Affiliation(s)
- Cherie Chu
- Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo, Hilo, HI
| | - Louis Lteif
- Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo, Hilo, HI
| | - Nicole Young
- Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo, Hilo, HI
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