Effects of Chronic Ethanol Administration on Disposition of Ethanol and its Metabolites and Drug-interaction

长期服用乙醇对乙醇及其代谢物的处置和药物相互作用的影响

基本信息

批准号：
16590540
负责人：
FUJIMIYA Tatsuya
金额：
$ 2.24万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

Acetaldehyde and acetate (AcT) are the first and second metabolites of ethanol and detected in the plasma. Acetaldehyde and acetate redistribution from hepatic to peripheral tissues was reported during ethanol metabolism. Chronic ethanol administration affects ethanol metabolism. However, the effects of chronic ethanol intoxication on the disposition of its metabolites were hardly examined. In this study, we conducted the pharmacokinetic studies on the effects on its metabolites. Seven - weeks old, male Wister rats fed a nutritionally adequate liquid-diet in which ethanol was provided by 21% (3g/dl) or 35% (5g/dl) of the total calories. These diets were originally formulated by Lieber and DeCarli. At the beginning of the study, all rats were given the control liquid-diet for 4 days. For the next 4 days, the rats were fed either the control liquid-diet or 3g/dl ethanol liquid-diet. The 3g/dl group received this ethanol concentration for 45 days, while the 5g/dl group received a diet containing 4g/dl of ethanol for the next 3 days, followed by 5g/dl diet for 42 days. To maintain a similar caloric intake among the groups, the groups were pair-fed. Liquid-diet consumption was adjusted daily according to the animal's body weight and the daily liquid-diet intake. A bolus of EtOH saline solution (0.5,1.0,2.0 g/kg) was injected intravenously. Blood EtOH and AcT concentrations were measured by using head-space gas chromatography. The elimination rate of ethanol and the steady-state concentration of acetate increased with chronic ethanol exposure.

乙醛和乙酸酯（ACT）是乙醇的第一和第二代谢产物，并在血浆中检测到。在乙醇代谢期间，报道了乙醛和乙酸盐从肝组织重新分布。慢性乙醇给药会影响乙醇代谢。但是，几乎没有检查慢性乙醇中毒对其代谢产物处置的影响。在这项研究中，我们就其代谢产物的影响进行了药代动力学研究。七个星期大的雄性北蜂鼠大鼠喂养营养充足的液体含量，其中乙醇由21％（3g/dl）或总卡路里的35％（5g/dl）提供。这些饮食最初是由Lieber和Decarli制定的。在研究开始时，将所有大鼠均允许对照液-DIET 4天。在接下来的4天中，将大鼠喂食对照液-DIET或3G/DL乙醇液体 - 液体。 3G/DL组接受了45天的乙醇浓度，而5G/DL组在接下来的3天内接受了含有4G/DL乙醇的饮食，然后进行5G/DL饮食，持续42天。为了在组之间保持类似的热量摄入量，这些组成对。每天根据动物的体重和每日液体摄入量调节液体饮用量。静脉注射的ETOH盐水溶液（0.5,1.0,2.0 g/kg）的推注。通过使用头部空间气相色谱法测量血液ETOH和ACT浓度。乙醇的消除率和乙酸盐的稳态浓度随慢性乙醇暴露而增加。

项目成果

期刊论文数量（24）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Pharmacokinetic Study of Ethanol and its Metabolites in Swift Increase in Alcohol Metabolism (SIAM) --Effect of cyanamide--

乙醇及其代谢物在酒精代谢迅速增加中的药代动力学研究（SIAM）--氰胺的作用--

DOI：
发表时间：
2005
期刊：
Japanese Journal of Alcohol Studies & Drug Dependence vol.40(4)
影响因子：
0
作者：
Kozawa;S.;et al.
通讯作者：
et al.

アルコール点滴静注時のアルコールと代謝産物の血中動態に関する研究-アルコール消失速度と血中酸濃度との関係-

静脉输注酒精时血液中酒精及代谢物的动态研究-酒精消失率与血酸浓度的关系-

DOI：
发表时间：
2005
期刊：
アルコールと医学生物学 25
影响因子：
0
作者：
I.Yuasa;K.Umetsu;S.Harihara;A.Kido;A.Miyoshi;N.Saitou;B.Dashnyam;F.Jin;G.Lucotte;P.K.Chattopadhyay;L.Henke;J.Henke;嶋本晶子他
通讯作者：
嶋本晶子他

Pharmacokinetic Study of Ethanol and its Metabolites in Swift Increase in Alcohol Metabolism (SIAM)

乙醇及其代谢物在酒精代谢迅速增加中的药代动力学研究 (SIAM)