Authors: Dechun Jiang Xiangrong Bai Qingxia Zhang Wei Lu Yuqin Wang Lin Li Markus Müller
Publish Date: 2009/09/16
Volume: 65, Issue: 12, Pages: 1187-
Abstract
VPA concentrations were measured in 287 epileptic patients who were genotyped for CYP2C192/3 and CYP2C93 Patients who were on monotherapy with VPA were divided into two groups a PPKmodel group n = 177 and a PPKvalid group n = 110 The PPK parameter values for VPA were calculated in the PPKmodel group by using the NONMEM software Ultimately a biological model and a final model were established Each model was then used to independently predict the concentrations of the PPKvalid group to validate the two modelsThere was a significant effect of the CYP2C19 and CYP2C9 genotypes on the pharmacokinetic PK variability P 001 in the final PPK model of CL/F The interindividual CL was calculated according to the final model CL/F = 00951 × 1 + e00267 × 3 − genotype + 00071 × age L/h The coefficient of variation CV omega CL/F of the final model was 293 while that of the biological model was 317 Based on the genotype the individual PK parameters can be calculated more accurately than before
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