摘要
目的:采用癫痫患者丙戊酸群体药动学参数结合贝叶斯(Bayesian)法估算癫痫患者丙戊酸的个体药动学参数;制定或优化欲达预期血药浓度所应实施的给药方案,使癫痫患者丙戊酸给药有效、合理、毒副作用小。方法:癫痫患者口服丙戊酸达稳态,取其每天早晨服药前10 min血样57人次,用荧光偏振免疫法(Fluorescence Polarization Immunoassay,FPIA)测得血清中丙戊酸和游离丙戊酸血药浓度谷值。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:按口服一房室一级吸收和消除的开放模型用Bayesian法估算得丙戊酸药动学参数清除率CL,平均值为(8.7±0.6)mL·h-1·kg-1,逐步回归方程:CL(mL·h-1·kg-1)=3.972+1.631X5+1.608X11;稳态血药浓度谷值Cp0逐步回归方程:Cp0(mg·L-1)=57.58-0.71X4-12.145X5+2.705X7+0.403X17。式中X4表示体重(kg), X5表示身高(cm) 体重(kg)比, X7表示每日每千克体重的给药剂量(mg·d-1·kg-1), X11表示当合并用苯妥英钠时系数为1,否则为0, X17表示血清肌酐(μmol·L-1)。实测丙戊酸稳态血药浓度谷值(52.4±5.4)mg·L-1与估算值(53.5±5.2)mg·L-1间差异无统计学意义,P>0.05。
OBJECTIVE To estimate the pharmacokinete the parameter of valproic acid(VPA) and administration with individuation by Bayesian and popular pharmacokinetics parameter, and to optimize administration with individuation. METHODS 57 blood samples of VPA on steady-state trough level were collected from epileptic patients, who continuously po-administrated VPA for a long time. The serum concentrations and free drug concentration of all the samples were determined by fluorescence polarization immunoassay(FPIA), respectively. Then individual pharmacokinetics parameters of VPA were estimated with Bayesian and popular pharmacokinetics parameters. And the influence of 18 factors such as sex, age etc on pharmacokinetics parameter and serum concentration was investigated through stepwise regression. Finally administration with individuation was optimized by the results and the therapeutic effect. RESULTS According to one-compartment open model with first-order absorption and elimination the individual pharmacokinetics parameters of VPA were worked out with Bayesian. The final result of individual pharmacokinetics parameter of VPA was CL =( 8.7 ± 0.6 ) mL·h -1 ·kg -1 ,The stepwise regression equation of CL was CL (mL·h -1 ·kg -1 )= 3.972 + 1.631 X_ 5 + 1.608 X_ 11 , The stepwise regression equation of C _ p0\} was: C _ p0\}(mg·L -1 )= 57.58 - 0.71 X_ 4 - 12.145 X_ 5 + 2.705 X_ 7 + 0.403 X_ 17 .In which X_ 4 was the body weight(kg), X_ 5 was ratio between the body height(cm) and the body weight(kg), X_ 7 was daily dose divided by body weight (mg·d -1 ·kg -1 ), X_ 11 was when VPA co-administrated with phenytoin coefficient 1 otherwise 0, X_ 17 was serum creatinine (μmol·L -1 ). There were no significant indifference between the average serum concentrations of VPA of epileptic patients estimated by Bayesian approach which was ( 53.5 ± 5.2 )mg·L -1 and the data actually assayed by FPIA which was ( 52.4 ± 5.4 )mg·L -1 , P > 0.05 . CONCLUSION Individual pharmacokinetics parameter of VPA can be estimated with Bayesian,and administration with individuation can be studied out and optimized by the Bayesian and the therapeutic effect.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2005年第4期324-329,共6页
Chinese Journal of Hospital Pharmacy
关键词
贝叶斯法
丙戊酸
个体化给药
荧光偏振免疫法
血药浓度
Bayesian
valprolc acid
administration with Individuation
fluorescence polarization immunoassay
drug concentration in serum
