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.

乙醛和乙酸盐 (AcT) 是乙醇的第一种和第二种代谢物，可在血浆中检测到。据报道，在乙醇代谢过程中，乙醛和乙酸盐从肝脏重新分配到外周组织。长期服用乙醇会影响乙醇代谢。然而，几乎没有研究慢性乙醇中毒对其代谢物的影响。在这项研究中，我们对其代谢物的影响进行了药代动力学研究。七周大的雄性 Wister 大鼠喂食营养充足的流质饮食，其中乙醇占总热量的 21% (3g/dl) 或 35% (5g/dl)。这些饮食最初是由利伯和德卡利制定的。研究开始时，所有大鼠均接受对照流质饮食 4 天。接下来的 4 天，给大鼠喂食对照流质饮食或 3g/dl 乙醇流质饮食。 3g/dl组接受该乙醇浓度45天，而5g/dl组在接下来的3天接受含有4g/dl乙醇的饮食，随后接受5g/dl饮食42天。为了保持各组之间相似的热量摄入，各组进行配对喂养。每天根据动物体重和每日流质饮食摄入量调整流质饮食消耗量。静脉内注射一团EtOH盐水溶液(0.5、1.0、2.0g/kg)。使用顶空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着长期乙醇暴露而增加。

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)