Vol.54 No.1 January 2006
Population pharmacokinetics of biapenem in patients and healthy subjects
Pharmacokinetic Laboratory, Pharmaceutical Development Department, Meiji Seika Kaisha, Ltd.,
760 Morooka-cho, Kouhoku-ku, Yokohama, Kanagawa, Japan
Abstract
Population pharmacokinetic parameters of biapenem (BIPM), a carbapenem antibiotic, were generated by a nonlinear mixed effects model using the NONMEM program based on plasma concentrations in patients and healthy subjects. A total of 384 plasma samples were collected from 66 subjects, and their demographic background data were recorded. The data obtained were analyzed using the two-compartment model. The covariates (age, weight [Wt], creatinine clearance [Ccr]) and one factor (the effect of disease) were tested for an effect on the pharmacokinetics of BIPM. Population pharmacokinetic parameters were not related to the effect of disease. Total clearance (CL) was found to be associated with Ccr, and the volume of distribution of the central compartment (V1) was associated with Wt. The volume of distribution of the peripheral compartment (V2) was not associated with Wt. The final formulae for the population mean parameters were: CL=0.0720×Ccr+3.04 (L/h), V1=0.0990×Wt (L), inter-compartmental clearance (Q) =13.5 (L/h), V2=7.00 (L). The validity of the model has been evaluated by the bootstrapping method. The time above the MIC's (T>MIC) were estimated from the plasma concentration profiles calculated based on population mean parameters and MIC's in order to create tables for establishment of dosing regimens for BIPM.
Key word
biapenem, population pharmacokinetics, NONMEM, Time above MIC
Received
September 13, 2005
Accepted
December 9, 2005
Jpn. J. Chemother. 54 (1): 7-17, 2006
