1996 Fiscal Year Final Research Report Summary
Biostatistical Modeling for Pharmacokinetics and Pharmacodynamics of Anticancer Agents and Application to Individualized Dosage Regimen
| Project/Area Number |
07557294
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 試験 |
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| Research Field |
Physical pharmacy
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| Research Institution | KOBE UNIVERSITY |
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Principal Investigator |
TANIGAWARA Yusuke Kobe University University Hospital Faculty of Medicine Associate Professor, 医学部附属病院, 助教授 (30179832)
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| Co-Investigator(Kenkyū-buntansha) |
OKUMURA Katsuhiko Kobe University University Hospital Faculty of Medicine Professor, 医学部附属病院, 教授 (60025707)
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| Project Period (FY) |
1995 – 1996
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| Keywords | Anticancer agents / Docetaxl / Pharmacokinetics / Pharmacodynamics / Population Pharmacokinetics / Clinical Pharmacology |
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| Research Abstract |
Pharmacokinetics and pharmacodynamics of docetaxl (Taxotere) have been investigated by a population analysis using the 662 plasma concentration data obtained from 102 Japanese patients who participated in the phase I and II clinical trials. Docetaxl disposition was described by a 3-compartment linear model at the dose range of 10-90 mg/m^2. NONMEN analysis showed that the docetaxl clearance was related to the body surface area (BSA,m^2) and serum albumin level (ALB,g/100ml) and inversely correlated with alpha_1-acid glycoprotein level (AAG,mg/100ml) and age. The patients having hepatic dysfunction (HEP1=1) indicated by the elevation of GOT or GPT greater than 60 IU/L showed 12% reduction in clearance. The population mean of clearance was described by the equation : CL=BSA (37.0-0.0629AAG-0.192AGE+0.542ALB) (1-0.124HEP1). The remaining interindividual variability was 26%. These results were comparable to those obtained in European and American population, suggesting no racial difference in the elimination of docetaxl. The relationships between pharmacokinetic characteristics and the dose limiting toxicity (myelosuppression) were described by a sigmoid Emax model. The area under the concentration-time curve (AUC) was a determining factor for the severity of myelosuppression. However, the efficacy was not correlated with the AUC values. The present findings are useful for optimizing docetaxl dosage.
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