| Project/Area Number |
60870093
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Kyoto University |
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Principal Investigator |
HORI Ryohei Kyoto University, 医学部, 教授 (40001036)
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| Co-Investigator(Kenkyū-buntansha) |
TANIGAWARA Yusuke Kyoto University, 医学部, 助手 (30179832)
IWAKAWA Seigo Kyoto University, 医学部, 助手 (50168548)
YASUHARA Masato Kyoto University, 医学部, 助手 (00127151)
KAMIYA Akira Kyoto University, 医学部, 助手 (90124792)
OKUMURA Katsuhiko Kyoto University, 医学部, 助教授 (60025707)
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| Project Period (FY) |
1985 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1986: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1985: ¥4,800,000 (Direct Cost: ¥4,800,000)
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| Keywords | 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 |
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| Research Abstract |
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.
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