1996 Fiscal Year Final Research Report Summary
Fundamental Studies on Population Pharmacokinetics of Alcohol and Alcohol-Drug Interaction
| Project/Area Number |
07670500
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Legal medicine
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
FUJIMIYA Tatsuya Kyoto Prefectural University of Medicine, Medicine, Associate Professor, 医学部, 助教授 (50219044)
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| Co-Investigator(Kenkyū-buntansha) |
OHBORA Yumiko Kyoto Prefectural University of Medicine, Medicine, Research Assistant, 医学部, 助手 (90079757)
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| Project Period (FY) |
1995 – 1996
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| Keywords | Alcohol / Pharmacokinetics / Population Pharmacokinetics / Drug-drug Interaction / Noncompetitive Inhibition |
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| Research Abstract |
Fundamental studies on population pharmacokinetics of alcohol and alcohol-drug interaction were conducted. At first, the technical problems of the pharmacokinetic analysis of alcohol disposition were studied using the Michaelis-Menten elimination kinetics models. The ordinary least-squares (OLS) method was compared with the Baysian least-squares (BLS) method. Correlation between the V_<max> and beta values, and between the V_<max> and K_m values, was seen when the parameter values were estimated by the OLS method. These results suggested that one-line fitting by the OLS method was not adequate for Michaelis-Mentan-type elimination kinetics analysis.
At second, the pharmacokinetic mechanism of the inhibition of ethanol metabolism by cyanamide, an inhibitor of mitochondrial aldehyde dehydrogenase, was studied. As a result, the estimated V_<max> values decreased by cyanamide treatment, whereas the K_m value did not change. Our results correspond to a noncompetitive-like inhibition of ethanol metabolism. This result is thought to be an example of alcohol-drug interaction.
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