Population pharmacokinetic model of valproate and prediction of valproate serum concentrations in children with epilepsy

被引:0
作者
Jiang, DC [1 ]
Wang, L [1 ]
机构
[1] Peking Univ, Hosp 1, Therapeut Drug Monitoring & Clin Toxicol Ctr, Dept Pediat, Beijing 100034, Peoples R China
关键词
pharmacokinetics; valproic acid; epilepsy; Bayes theorem; USC*PACK software;
D O I
暂无
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
AIM: Using sparse data of valproate (VPA) serum concentrations to build a population pharmacokinetic (PPK) model of VPA in Chinese children. with epilepsy and to predict serum concentrations for new patients using a Bayesian approach. METHODS: Two hundred epileptic children, whose VPA serum concentrations were collected, were divided randomly into two groups (A and B, n=100 each). The PPK parameter values of group A were calculated to establish a PPK Model by using the NPEM Program of USC*PACK software. Based on it, VPA serum concentrations of group B were predicted with the Bayesian Fitting Program of the USC*PACK software. To assess the accuracy and precision of prediction, a paired-comparisons t-test was run between predicted and observed concentrations, and then the mean prediction error (MPE), mean square prediction error (MSPE), root mean square prediction error (RMSPE), and coincidence rates for different percentages of prediction error were all calculated. RESULTS: Optimum PPK parameters were: Ka, 2.522+/-2.743 h(-1); Vs, 0.329+/-0.496 L/kg; and Ke1, 0.0438+/-0.0384 ha(-1). For group B, there was no significant difference between predicted and observed concentrations. MPE was -0.43 mg/L, MSPE was 115.40 (mg/L)(2), and RMSPE was 5.47 mg/L. The coincidence rates for percentages of prediction error, which were less than 5 %, 10 %, 15 %, 20 %, 25 %, and 30 %, were 62 %, 74 %, 82 %, 85 %, 89 %, and 93 %, respectively. CONCLUSION: A PPK model of VPA in epileptic children was successfully established. Based on it, VPA serum concentrations can be predicted accurately with a Bayesian approach.
引用
收藏
页码:1576 / 1583
页数:8
相关论文
共 34 条
[21]   Amikacin Bayesian forecasting in critically ill patients with sepsis and cirrhosis [J].
Lugo, G ;
CastanedaHernandez, G .
THERAPEUTIC DRUG MONITORING, 1997, 19 (03) :271-276
[22]   Failure of traditional trough levels to predict tacrolimus concentrations [J].
Macchi-Andanson, M ;
Charpiat, B ;
Jelliffe, RW ;
Ducerf, C ;
Fourcade, N ;
Baulieux, J .
THERAPEUTIC DRUG MONITORING, 2001, 23 (02) :129-133
[23]   SINGLE AND CHRONIC DOSE PHARMACOKINETIC STUDIES OF SODIUM VALPROATE IN EPILEPTIC PATIENTS [J].
MIHALY, GW ;
VAJDA, FJ ;
MILES, JL ;
LOUIS, WJ .
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 1979, 16 (01) :23-29
[24]   PHARMACOKINETIC INTERACTION BETWEEN VALPROIC ACID AND PHENOBARBITAL [J].
POKRAJAC, M ;
MILJKOVIC, B ;
VARAGIC, VM ;
LEVIC, Z .
BIOPHARMACEUTICS & DRUG DISPOSITION, 1993, 14 (01) :81-86
[25]   Prediction of valproate serum concentrations in adult psychiatric patients using Bayesian model estimations with NPEM2 population pharmacokinetic parameters [J].
Puentes, E ;
Puzantian, T ;
Lum, BL .
THERAPEUTIC DRUG MONITORING, 1999, 21 (03) :351-354
[26]   Pharmacokinetic interactions between antiepileptic drugs - Clinical considerations [J].
Riva, R ;
Albani, F ;
Contin, M ;
Baruzzi, A .
CLINICAL PHARMACOKINETICS, 1996, 31 (06) :470-493
[27]   SOME SUGGESTIONS FOR MEASURING PREDICTIVE PERFORMANCE [J].
SHEINER, LB ;
BEAL, SL .
JOURNAL OF PHARMACOKINETICS AND BIOPHARMACEUTICS, 1981, 9 (04) :503-512
[28]   Population pharmacokinetics - A regulatory perspective [J].
Sun, H ;
Fadiran, EO ;
Jones, CD ;
Lesko, L ;
Huang, SM ;
Higgins, K ;
Hu, CP ;
Machado, S ;
Maldonado, S ;
Williams, R ;
Hossain, M ;
Ette, EI .
CLINICAL PHARMACOKINETICS, 1999, 37 (01) :41-58
[29]  
*USC, 1995, USC PACK COMP PROGR
[30]  
WANG L, 2002, PEDIAT PHARM DRUG TH, P210