Pharmacokinetic/pharmacodynamic analysis of meropenem, by Monte Carlo simulation, in both plasma and cerebrospinal fluid in patients with cerebral hemorrhage after external ventricular drainage .

Abstract

Patients with cerebral hemorrhage are often prone to intracranial infection, and meropenem is recommended for treatment. But whether the widely used dosing regimen (1 g, 2-hour infusion, every 12 hours) is suitable for antibiotic therapy is still unclear. The purpose of this study was to perform pharmacokinetic/pharmacodynamic (PK/PD) analyses of meropenem in both plasma and cerebrospinal fluid (CSF) in these patients. Ten patients were enrolled in the present study. The blood samples and CSF samples were taken at predetermined time points and determined by our previously developed HPLC method. Pharmacokinetic parameters were then calculated, and the probability of target attainment (PTA) was calculated by the time that drug concentrations were above the minimum inhibitory concentration (%T>MIC). The peak meropenem concentration (Cmax) of 17.79 ± 3.38 μg/mL in plasma was reached at 2 hours, and the area under the curve (AUC) was 46.95 ± 4.37 h×μg/mL. The Cmax of 6.51 ± 1.11 μg/mL in CSF was reached at 3.50 ± 0.53 hours, and the AUC was 24.53 ± 4.28 h×μg/mL. The average penetration rate of meropenem in these patients was 52.25%. In the case where the MIC value was ≤ 1 μg/mL and using 40%T>MIC as a PK/PD index, the PTA of meropenem in both plasma and CSF were able to provide good coverage with MIC ≤ 1 μg/mL. In conclusion, this is the first study on the PK/PD analysis of meropenem in both plasma and CSF in patients with cerebral hemorrhage. The results will assist in selecting appropriate dosing regimens of meropenem in these patients.