摘要
目的采用丙戊酸(VPA)群体药动学参数结合Bayesian法估算癫疒间患者VPA的个体药动学参数。方法60例癫疒间患者口服VPA达稳态,取其每天早晨服药前10 min血样,用荧光偏振免疫法(FPIA)测得血清中VPA血药浓度谷值。用Bayesian法估算其药动学参数,并用逐步回归法分析个体的性别、年龄等18种因素对其药动学参数的影响。结果按口服一级吸收和消除的一房室开放模型用Bayesian法计算得VPA药动学参数清除率CL为(8.98±2.50)mL.h-1.kg-1,逐步回归CL方程:CL=5.858+1.423X5+1.593X11,式中X5表示身高(cm)体重(kg)比,X11表示当合并用苯妥英钠时系数为1,否则为0。估算的个体稳态VPA血药浓度谷值平均为(54.19±20.50)mg.L-1,实测结果平均为(53.58±20.85)mg.L-1,估算结果与实测结果之间无显著性差异(P>0.05)。结论可采用Bayesian法估算癫疒间患者VPA动力学参数CL和预测癫疒间患者个体稳态VPA血药浓度谷值;当癫疒间患者身高体重比增加或合并使用苯妥英时VPA动力学参数CL增加。
AIM To estimate the individual pharmacokinetic parameters of valporinic proach. METHODS Sixty blood samples of VPA on steady-state acid（VPA） by Bayesian aptrough level were collected from epileptic patients. All the samples were assayed by fluorescence polarization immunoassay （FPIA） to determine VPA concentration in serum on steady-state trough level. Then individual pharmacokinetic parameters of VPA were estimated by Bayesian approach. And the influence of 18 factors such as sex, age, etc. on pharmacokinetic parameters was analyzed through stepwise regression. RESULTS According to one-compartment open model with first-order absorption and elimination, the individual pharmacokinetic parameters of VPA were worked out by Bayesian approach. The final result of individual pharmacokinetic parameters of VPA was CL = （8.98 ± 2.50） mL·h ^- 1· kg^- 1. The stepwise regression equation of CL was CL = 5. 858 ＋ 1.423 X5 ＋ 1.593 X11. In which X5 was the ratio between the body height（cm） and the body weight（kg）, X11 referred to coefficient being 1 otherwise 0 when VPA co-administrated with phenytoin. The average serum concentrations of VPA in epileptic patients estimated by Bayesian approach were （54.19 ± 20.50） mg· L^-1 and the data actually assayed by FPIA was （53.58 ± 20.85）mg·L^-1, with no significant difference（P 〉 0.05）. CONCLUSION The Bayesian approach can be adapted for estimating individual pharmacokinetic parameters of VPA, and forecasting serum concentration of VPA in epileptic patients. CL of VPA in epileptic patients will increase if ratio between body height and body weight of epileptic patients rises, or co-administrated with phenytoin.
出处
《中国临床药学杂志》
CAS
2005年第5期278-281,共4页
Chinese Journal of Clinical Pharmacy
关键词
丙戊酸
癫癎
Bayesian法
群体药动学
荧光偏振免疫法
血药浓度
valproic acid
epilepsy
Bayesian
population pharmacokinetics
fluorescence polarization immunoassay
serum concentration
