Fundamental Studies on Population Pharmacokinetics of Alcohol and Alcohol-Drug Interaction

酒精和酒精-药物相互作用的群体药代动力学基础研究

• 批准号: 07670500
• 负责人: FUJIMIYA Tatsuya
• 金额: $ 1.22万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670500/
• 关键词: Alcohol; Pharmacokinetics; Population Pharmacokinetics; Drug-drug Interaction; Noncompetitive Inhibition

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.

对酒精和酒精-药物相互作用的群体药代动力学进行了基础研究。首先，利用Michaelis-Menten消除动力学模型研究了酒精处置的药代动力学分析的技术问题。将普通最小二乘法（OLS）与贝叶斯最小二乘法（BLS）进行比较。当通过 OLS 方法估计参数值时，可以看到 V_<max> 和 beta 值之间以及 V_<max> 和 K_m 值之间的相关性。这些结果表明OLS方法的单线拟合不足以进行米氏-门坦型消除动力学分析。 其次，研究了线粒体乙醛脱氢酶抑制剂氰胺抑制乙醇代谢的药代动力学机制。结果，估计的 V_<max> 值因氰胺处理而降低，而 K_m 值没有变化。我们的结果对应于乙醇代谢的非竞争性抑制。这一结果被认为是酒精与药物相互作用的一个例子。

项目成果

藤宮龍也: "アルコールの動態解析の問題点-ベイズ最小二乗法の試み-" アルコールと医学生物学. 15. 11-15 (1995)

Tatsuya Fujimiya：“酒精动态分析中的问题 - 贝叶斯最小二乘法的尝试”《酒精与医学生物学》15. 11-15 (1995)。

Tatsuya Fujimiya: "Problems in Pharmacokinetic Analysis of Alcohol Disposition:A Trial of the Bayesion Least-Squores Method" Alcoholism:Clinical and Experimental Ressearch. 20・1. 2A-6A (1996)

Tatsuya Fujimiya：“酒精处置的药代动力学分析问题：贝叶斯最小二乘法的试验”酒精中毒：临床和实验研究（1996）。

Tatsuya Fujimiya: "Noncompetitive-Like Inbibition of Ethanol Elomination by Cyanamide Treatment:Phermacokinetic Study" Alcoholism:Clinical and Experimental Research. 20・9. 278A-283A (1996)

Tatsuya Fujimiya：“氰酰胺处理对乙醇消除的非竞争性抑制：药代动力学研究”酒精中毒：20・9 278A-283A。

藤宮龍也: "シアナマイドによる血中アルコール消失への薬物動態学的影響" アルコールと医学生物学. 16. 6-9 (1996)

Tatsuya Fujimiya：“氰胺对血液酒精消除的药代动力学影响”《酒精与医学生物学》16. 6-9 (1996)。

T.Fujimiya, K.Uemura, Y.Ohbora & S.Komura: "Problems in Pharmacokinetics Analysis of Alcohol Disposition : A Trial of the Baysian Least-Squares Method." Alcoholism : Clinical and Experimental Research. 20 (1). 2A-6A (1996)

T.Fujimiya、K.Uemura、Y.Ohbora