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Population Pharmacokinetic Analysis and Dosing Regimen Optimization of Meropenem in Adult Patients

From the Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut. This study was funded by AstraZeneca Pharmaceuticals L.P. (Wilmington, Del). Dr Nicolau and Dr Kuti have received research funding from AstraZeneca and act as consultants. Other authors have no conflict of interest.

The objectives of this study were to develop a meropenem population pharmacokinetic model using patient data and use it to explore alternative dosage regimens that could optimize the currently used dosing regimen to achieve higher likelihood of pharmacodynamic exposure against pathogenic bacteria. We gathered concentration data from 79 patients (ages 18-93 years) who received meropenem 0.5, 1, or 2 g over 0.5- or 3-hour infusion every 8 hours. Meropenem population pharmacokinetic analysis was performed using the NONMEM program. A 2-compartment model fit the data best. Creatinine clearance, age, and body weight were the most significant covariates to affect meropenem pharmacokinetics. Monte Carlo simulation was applied to mimic the concentration-time profiles while 1 g meropenem was administrated via infusion over 0.5, 1, 2, and 3 hours. The 3-hour prolonged infusion improved the likelihood of obtaining both bacteriostatic and bactericidal exposures most notably at the current susceptibility breakpoints.

Key Words: Meropenem • population pharmacokinetics • pharmacodynamics • dosing

Address for reprints: David P. Nicolau, PharmD, FCCP, Center for Anti-Infective Research and Development, Hartford Hospital, 80 Seymour Street, Hartford, CT 06102; e-mail: dnicola{at}harthosp.org.

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