Nonlinear Mixed Effects Model Analysis of the Pharmacokinetics of Aripiprazole in Healthy Japanese Males(Biopharmacy)

概要

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The population pharmacokinetic parameters of aripiprazole in healthy Japanese males were estimated using a nonlinear mixed effects model (NONMEM) program. Pharmacokinetic data for population analysis were obtained from the single-dose (24 subjects), multiple-dose (15 subjects), and itraconazole-coadministration (27 subjects) trials. The time course of plasma aripiprazole concentration following oral administration was well described by a two-compartment model with first-order input. The mean values of the absorption lag time (ALAG) and absorption rate constant (KA) were estimated to be 0.805h and 2.65h^<-1>, respectively. The mean volume of the central (V_1/F) and peripheral (V_2/F) compartment was 3.84 and 1.54l/kg, respectively, and the mean value of inter-compartment clearance (Q/F) was 0.168l/h/kg. Oral clearance (CL/F) was estimated to be 0.0645l/h/kg in the group with CYP2D6^*1/^*1, ^*1/^*2 and ^*2/^*2. The decrease in CL/F was estimated to be 0.0135l/h/kg in the group with CYP2D6^*1/^*5, ^*1/^*10, ^*2/^*5, ^*2/^*10, and ^*2/^*41, and 0.0293l/h/kg in the group with CYP2D6^*5/^*10, ^*10/^*10, and ^*41/^*41. The plasma concentration of aripiprazole was increased by coadministration of itraconazole, and the decrease in CL/F was estimated to be 0.0181l/h/kg.
公益社団法人日本薬学会の論文
2007-11-01