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

Abstract

Purpose: The aim of this study was to investigate the population pharmacokinetic (PK) profile of mero-penem in Korean patients with acute infections.

Methods: The study included 37 patients with acreat-inine 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 (relativeSE) for weight-normalized clearance (CL) and Vd were 0.266 L/h/kg (12.29%) and 0.489L/kg(11.01%), respectively. Meropenem CL was sign ificantly influenced bytheserum creatinine level,which explained11% oftheinter individ- ual CKvariability. 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 simulationresultsindicate thatthecurrentmerope-nem dosingregimenmaybesuboptimalinpatients infected withnormaloraugmentedrenalfunction.

Implications: Prolonged infusions of meropenem over atleast 2 hours should beconsidered,especially in patientswithaugmentedrenalfunctionand those infectedwithpathogensforwhichtheminimum inhibitory meropenemconcentrationis >1 mg/mL. Our results suggest anindividualized meropenem dosing regimenforpatientswithabnormalrenal function andthoseinfectedwithpathogens withdecreased invitrosusceptibility.(ClinTher. 2018;40:1384 1395)