Setting up population pharmacokinetics/pharmacodynamics model of VPA in children with epilepsy by NONMEM software
- VernacularTitle:用NONMEM法建立中国癫痫儿童丙戊酸钠的群体药动学/药效学结合模型
- Author:
Dechun JIANG
;
Li WANG
;
Wei LU
- Publication Type:Journal Article
- Keywords:
epilepsy;
children;
population pharmacokinetics;
population pharmacodynamics;
valproate;
NONMEM software
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2004;0(11):-
- CountryChina
- Language:Chinese
-
Abstract:
AIM: To set up population pharmacokinetics/pharmacodynamics (PPK/PD) model of valproate (VPA) in children with epilepsy in China, and promote reasonable use of antiepileptic drugs(AEDs)in clinical practice. METHODS: Sparse data of VPA serum concentrations from 246 pediatric children were collected. These patients were divided into three groups: PPK-Model group ([WTBX]n=146), to calculate PPK parameter values of VPA and set up a PPK model; PPK-Valid group ([WTBX]n=100), to valid the PPK model; and PPD group ([WTBX]n=69), to set up PPK/PD model. Based on the data of PPK-Model group and PPK-Valid group, a PPK model of VPA in children with epilepsy in China was successfully set up by using NONMEM software by ourselves. Now, using the data of 69 patients in PPD group who were on VPA monotherapy and this PPK model, we set up PPK/PD model by NONMEM software. Efficacy of epilepsy treatment was divided into 5 grades according to the percentage of seizure frequency decreased (PSFD%): grade 1: PSFD% was 100%; grade 2: PSFD% was 75%-100%; grade 3: PSFD% was 50%-75%; grade 4: PSFD% was 25%-50%; grade 5: PSFD% was less than 25%. The quantitive relationship between the VPA serum concentrations and the probability for its efficacy score was characterized by Logistic regression analysis with NONMEM. RESULTS: Logistic regression analysis showed that, VPA serum concentrations and the probability for its efficacy grades 5, 4, 3, 2, and 1 were (23 ?g?ml -1, 5, 50%), (30 ?g?ml -1, 4, 32.3%), (50 ?g?ml -1, 3, 26.3%), (65 ?g?ml -1, 2, 36.5%), (78 ?g?ml -1, 1, 50%), and (100 ?g?ml -1, 1, 84.2%)respectively. CONCLUSION: A PPK/PD model of VPA in children with epilepsy in China is successfully established by using NONMEM software, and the probability of efficacy grade for any concentration can be calculated. It will be valuable to facilitate individualized dosage regimen.
