Application of population pharmacokinetics to the individualization of drug dosage regimen.

我们估计了日本患者的群体药代动力学参数，并制定了个体化给药方案。1)估计了日本患者丙戊酸、卡马西平、苯妥英、地高辛和茶碱的群体平均药代动力学参数、个体间变异和个体内变异。利用扩展最小二乘法编制了数据分析程序。本研究表明，治疗性药物监测等观察数据可用于估计群体药动学参数。用该方法评价了联合用药、病情、肾功能、肝功能和/或年龄对药代动力学的影响。总体参数是个体化给药方案的关键，影响个体药代动力学的预测效果。采集日本45家医院的血药浓度数据，并将估计参数作为日本患者的标准。2)采用贝叶斯非线性最小二乘拟合法，只需一次血药浓度即可估算个体药动学参数。估算的参数可用于模拟血药浓度-时间分布和制定给药方案。这种个体化方法有望提高治疗药物监测的临床意义。

We estimated the population pharmacokinetic parameters in Japanese patients and developed the individualization method of drug dosage regimen.1) Population pharmacokinetic parameters, which quantify population mean kinetics, interindividual variability, and intraindividual variability for a particular patient population, of valproic acid, carbamazepine, phenytoin, digoxin, and theophylline were extimated in Japanese patients. The data analysis program was also developed using extended least squares algorithm. The present investigation showed that the observational data such as therapeutic drug monitoring data can be utilized to estimate the population pharmacokinetic parameters. The influences of combination drug, disease state, renal function, hepatic function, and/or age upon pharmacokinetics were also evaluated by this approach. The population parameters are essential to the individualization of drug dosage regimen and affect the predictive performance of individual pharmacokinetics. The plasma concentration date were collected from 45 hospital in Japan, and the estimated parameters are regarded as the standard of Japanese patients.2) The individual pharmacokinetic parameters were estimated using only one plasma concentration measurement by the Bayesian nonlinear least squares fitting. The estimated parameters are useful to simulate the plasma concentration - time profile and develop the drug dosage regimen. This individualization method is expected to improve the clinical significance of therapeutic drug monitoring.