Population Pharmacokinetic Analysis of Meropenem After Intravenous Infusion in Korean Patients With Acute Infections

Purpose

The aim of this study was to investigate the population pharmacokinetic (PK) profile of meropenem in Korean patients with acute infections.

Methods

The study included 37 patients with a creatinine clearance ≤50 or >50 mL/min who received a 500- or 1000-mg dose of meropenem, respectively, infused intravenously over 1 hour every 8 hours. Blood samples were collected before and at 1, 1.5, and 5 hours after the start of the fourth infusion. The population PK analysis was conducted by using nonlinear mixed effect modeling software (NONMEM). Monte-Carlo simulations were performed to identify optimal dosing regimens.

Findings

Thirty-seven subjects completed the study. Meropenem PK variables were well described by using a one-compartment model. The typical values (relative SE) for weight-normalized clearance (CL) and V_d were 0.266 L/h/kg (12.29%) and 0.489 L/kg (11.01%), respectively. Meropenem CL was significantly influenced by the serum creatinine level, which explained 11% of the interindividual CK variability. The proposed equation to estimate meropenem CL in Korean patients was as follows: CL (L/h)?=?0.266?×?weight?×?serum creatinine/0.74]^–1.017_. The simulation results indicate that the current meropenem dosing regimen may be suboptimal in patients infected with normal or augmented renal function.

Implications

Prolonged infusions of meropenem over at least 2 hours should be considered, especially in patients with augmented renal function and those infected with pathogens for which the minimum inhibitory meropenem concentration is >1 μg/mL. Our results suggest an individualized meropenem dosing regimen for patients with abnormal renal function and those infected with pathogens with decreased in vitro susceptibility.