title: Population Pharmacokinetics and Pharmacodynamics of Meropenem in Nonobese, Obese, and Morbidly Obese Patients.
abstract: The study objective was to evaluate meropenem population pharmacokinetics and pharmacodynamics in nonobese, obese, and morbidly obese patients. Forty adult patients-11 nonobese (body mass index [BMI] < 30 kg/m2), 9 obese (30 kg/m2≤ BMI < 40 kg/m2), and 20 morbidly obese (BMI ≥ 40 kg/m2)-received meropenem 500 mg every 6 hours (q6h), q8h, or q12h or 1 g q6h or q8h, infused over 0.5 hour. Population pharmacokinetic modeling was performed using NONMEM, and 5000-patient Monte-Carlo simulations were performed to calculate probability of target attainment (PTA) for 5 dosing regimens, infused over 0.5 and 3 hours, using fT>MIC of 40%, 54%, and 100% of the dosing interval. A 2-compartment linear-elimination model best described the serum concentration-time data, and creatinine clearance was significantly associated with systemic clearance. Pharmacokinetic parameters were not significantly different among patient groups. In patients with creatinine clearances ≥50 mL/min, all simulated dosing regimens achieved >90% PTA at 40% fT>MIC in all patient groups at MICs ≤2 mg/L. Only 500 mg q8h, infused over 0.5 hour, did not achieve >90% PTA at 54% fT>MIC in nonobese and morbidly obese patients. At 100% fT>MIC, 1 g q6h and 2 g q8h, infused over 3 hours, reliably achieved >90% PTA in all patient groups. Meropenem pharmacokinetics are comparable among nonobese, obese, and morbidly obese patients. Standard dosing regimens provide adequate pharmacodynamic exposures for susceptible pathogens at 40% and 54% fT>MIC, but prolonged infusions of larger doses are needed for adequate exposures at 100% fT>MIC. Dosage adjustments based solely on body weight are unnecessary.
authors.affiliation: Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul, South Korea.
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Chung
authors.affiliation: Department of Pharmacy, Franciscan St. Francis Health, Indianapolis, IN, USA.
authors.forename: S Christian
authors.initials: SC
authors.lastname: Cheatham
authors.affiliation: Department of Pharmacy, Eskenazi Health, Indianapolis, IN, USA.
authors.forename: Megan R
authors.initials: MR
authors.lastname: Fleming
authors.affiliation: Division of Pharmacy Practice and Administrative Sciences, James L. Winkle College of Pharmacy, University of Cincinnati Academic Health Center, Cincinnati, OH, USA.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Healy
authors.affiliation: Department of Pharmacy Practice, Purdue University College of Pharmacy, Indianapolis and West Lafayette, IN, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Kays
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001827:Body Height; D015992:Body Mass Index; D001835:Body Weight; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008954:Models, Biological; D009010:Monte Carlo Method; D009765:Obesity / Q000378:metabolism*; D009767:Obesity, Morbid / Q000378:metabolism; D013845:Thienamycins / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D003404:Creatinine; D000077731:Meropenem
keywords: Monte Carlo simulation; NONMEM; meropenem; obesity; pharmacokinetics