1988 Fiscal Year Final Research Report Summary
Effect of aldehyde dehydrogenase deficiency of ethanol elimination after peroral of intravenous administrations
| Project/Area Number |
62480184
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Legal medicine
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| Research Institution | Kobe University |
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Principal Investigator |
MIZOI Yasuhiko Kobe University School of Medicine, Proffessor, 医学部, 教授 (00030809)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUNAGA Tatsushige Kobe University School of Medicine, Research Associate, 医学部, 助手 (70156800)
ADACHI Junko Kobe University School of Medicine, Research Associate, 医学部, 助手 (40030887)
FUJIWARA Satoshi Kobe University School of Medicine, Assistant Proffessor, 医学部, 講師 (20173487)
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| Project Period (FY) |
1987 – 1988
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| Keywords | Pharmakokinetics / first pass metabolism / aldehyde dehydrogenase / intravenous infusion / ミカエリスメンテン速度式 / コンパートメントモデル |
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| Research Abstract |
Japanese healthy male volunteers were divided into two groups, i.e., a normal aldehyde dehydrogenase (ALPH) group with a low Km isozyme of ALDN and a deficient group.
In Experiment I, the subjects received 0.1 and/or 0.4 g/kg doses of ethanol perorally and intravenously in different days. After a light meal. 0.1 g/kg dose of ethanol was administered as well as the former. At the dose of 0.4 g/kg, the blood ethanol curve became pseudolinear and followed curvilinear. No marked difference was noted in the elimination rate between in the both administrations, and the decreases of the areas under the curve (AUC) were 13 % and 22 % in subjects with the normal and deficient ALDH, respectively. At the dose of 0.1 g/kg, the blood ethanol curve became curvilinear after reaching a peak value. The decreases of the AUC were 35 % and 33 %, respectively. High blood acetaldehyde levels over 10 M were observed only in the deficient subjects. After a meal, blood ethanol levels became low and the AUC decreased conspicuously in peroral administration. The differences in the AUC between peroral and intravenous administrations were apparent when a lower dose of ethanol was used. The proportion of the first pass effect in the ethanol metabolism is relatively low. After a meal, a delay of absorption and a decrease in its efficiency lead to the low ethanol levels and the decrease of the AUC.
In Experiment II , 0.1 g/kg of ethanol was infused into the other twelve subjects. Ethanol elimination curves were fitted to the one compartment open nodel utilizing Michaelis-Menten elimination kinetics. The peak levels of the blood ethanol varied from 2.8 to 9.4 mM among the subjects. Apparent Km and Vmax values differed individually, the rate and volume of diffusion are also important factors in ethanol elimination.
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