Investigation of valproic acid-carbamazepine interaction by nonlinear mixed effect modeling in Chinese epilepsy patients

摘要

The study is to investigate the valproic acid (VPA)-carbamazepine (CBZ) interaction in Chinese epilepsy patients. Nonlinear mixed effects modeling (NONMEM) was used to estimate the effects of VPA-CBZ interaction on clearance values from 722 patients that received the administration of VPA and/or CBZ during their clinical routine care. The final model describing VPA clearance was: CL=0.00726cebtre bit TBW~(0.890)centre not(1-18.1DOSE)centre not1.36~(CBZ)centre nit1.22~(CHILD). The final model describing CBZ clearance was CL=1.21centre notDOSE~(0.409centre notTBW(0.292)centre not1.16~(VPA)centre notcentre not0.845~(ELDER), where CL is clearance (Lcentre not h~(-1) ), TBW is total body weight (kg), DOSE is daily dosage (g/kg/d), CHILD is the patient under 6 and ELDER is the patient over 60. CBZ=1 for the patients with concomitant administration of CBZ, otherwise CBZ=0. Concomitant administration of both VPA and CBZ resulted in 36% increase of VPA clearance and 16% increase of CBZ when VPA daily dose was greater than