title: Population pharmacokinetic modeling of oxcarbazepine active metabolite in Chinese patients with epilepsy.
abstract: The aim of the study was to develop a population pharmacokinetic (PPK) model of oxcarbazepine and optimize the treatment of oxcarbazepine in Chinese patients with epilepsy. A total of 108 oxcarbazepine therapeutic drug monitoring samples from 78 patients with epilepsy were collected in this study. The pharmacologically active metabolite 10,11-dihydro-10-hydrocarbamazepine (MHD) was used as the analytical target for monitoring therapy of oxcarbazepine. Patients' clinical data were retrospectively collected. The PPK model for MHD was developed using Phoenix NLME 1.2 with a non-linear mixed-effect model. MHD pharmacokinetics obeys a one-compartment model with first-order absorption and elimination. The effect of age, gender, red blood cell count, red blood cell specific volume, hemoglobin (HGB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and serum creatine were analyzed. Bootstrap and data splitting were used simultaneously to validate the final PPK models. The mean values of volume of distribution and clearance of MHD in the patients were 14.2 L and 2.38 L h(-1), respectively. BUN and HGB influenced the MHD volume of distribution according to the following equation: V = tvV × (BUN/4.76)(-0.007) × (HGB/140)(-0.001) × e (ηV) . The MHD clearance was dependent on ALT and gender as follows: CL = tvCL × (ALT/30)(0.181) × (gender) × 1.083 × e (ηCL). The final PPK model was demonstrated to be suitable and effective and it can be used to evaluate the pharmacokinetic parameters of MHD in Chinese patients with epilepsy and to choose an optimal dosage regimen of oxcarbazepine on the basis of these parameters.
authors.affiliation: Department of Clinical Pharmacology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, People's Republic of China. haoyyl0902@163.com.
authors.forename: Yunli
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Clinical Pharmacology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, People's Republic of China.
authors.forename: Quanying
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Clinical Pharmacology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, People's Republic of China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Pharmaceutics, Soochow University Affiliated Children's Hospital, Suzhou, 215003, People's Republic of China.
authors.forename: Chengzhe
authors.initials: C
authors.lastname: Lv
authors.affiliation: Suzhou Institute for Food and Drug Control, Suzhou, 215104, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Hao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D044466:Asian People; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D016903:Drug Monitoring / Q000379:methods; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D000078330:Oxcarbazepine; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D002220:Carbamazepine; D000078330:Oxcarbazepine
keywords: Epilepsy; MHD; Oxcarbazepine; Population pharmacokinetics