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

群体药代动力学在个体化药物剂量方案中的应用。

基本信息

批准号：
60870093
负责人：
HORI Ryohei
金额：
$ 4.22万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research
财政年份：
1985
资助国家：
日本
起止时间：
1985 至 1986
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-60870093/
关键词：
population pharmacokinetics therapeutic drug monitoring drug dosage regimen valproic acid carbamazepine; phenytoin digoxin ジゴキシンテオフィリン PHARMACOKINETICS POPULATION ベイズ理論 THERAPEUTIC DRUG MONITORING THEOPHYLLINE VALPROIC ACID

项目摘要

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.

我们估计了日本患者的群体药代动力学参数，并开发了药物剂量方案的个体化方法。1）群体药代动力学参数，其量化了特定患者群体的丙戊酸、卡马西平、苯妥英、地高辛和茶碱的群体平均动力学、个体间变异性和个体内变异性。利用扩展最小二乘法编制了数据分析程序。目前的研究表明，观察数据，如治疗药物监测数据，可以用来估计群体药代动力学参数。还通过该方法评价了联合用药、疾病状态、肾功能、肝功能和/或年龄对药代动力学的影响。群体参数是个体化给药方案的重要参数，影响个体药代动力学的预测性能。收集日本45家医院的血药浓度数据，并将估计的参数作为日本患者的标准。2）采用贝叶斯非线性最小二乘法拟合，仅用一次血药浓度测量值估计个体药动学参数。估计的参数可用于模拟血浆浓度-时间曲线和开发药物给药方案。这种个体化方法有望提高治疗药物监测的临床意义。