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

乙醛和乙酸（AcT）是乙醇的第一和第二代谢物，在血浆中检测到。据报道，乙醇代谢过程中乙醛和醋酸盐从肝脏再分布到外周组织。慢性给药影响乙醇代谢。然而，慢性乙醇中毒对其代谢物处置的影响几乎没有检查。在本研究中，我们对其代谢产物的影响进行了药代动力学研究。7周大的雄性Wister大鼠喂食营养充足的液体食物，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。在研究开始时，所有大鼠给予4 d的对照液体饲料。在接下来的4天里，大鼠分别饲喂对照液体饲料和3g/dl乙醇液体饲料。3g/dl组连续45天饲喂该浓度乙醇，5g/dl组连续3天饲喂含4g/dl乙醇的饲粮，随后连续42天饲喂含5g/dl乙醇的饲粮。为了保持各组之间相似的热量摄入，各组被成对喂食。根据动物的体重和每日液体饲料的摄入量，每日调整液体饲料的摄入量。静脉注射EtOH生理盐水（0.5、1.0、2.0 g/kg）。采用顶空气相色谱法测定血EtOH和AcT浓度。乙醇的消除速率和醋酸盐的稳态浓度随着乙醇的长期暴露而增加。

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.