Tilstone W J, Reavey P C
Res Commun Chem Pathol Pharmacol. 1978 Feb;19(2):233-42.
The presence and mechanism of synergism of action between ethanol and amylobarbitone, phenobarbitone or methaqualone was determined by application of simple pharmacokinetic models to log dose-response curves and plasma concentration-time curves for the hypnotics alone or when ethanol was given concurrently. For all three hypnotics, ethanol was found to increase the duration of hypnosis, but the mechanism of action was different for each. A sub-hypnotic dose of ethanol increased the volume of distribution of amylobarbitone and the consequent reduction in fractional elimination prolonged the half-life of the hypnotic. The distribution and elimination of methaqualone were not affected by ethanol, but there was a sensitisation of the target organ, shown by a reduced minimum effective dose. The minimum effective dose of phenobarbitone was also reduced by ethanol, but in addition, the rate of elimination of phenobarbitone was increased after the period of hypnosis.
通过将简单的药代动力学模型应用于单独使用催眠药或同时给予乙醇时的对数剂量反应曲线和血浆浓度-时间曲线,确定了乙醇与戊巴比妥、苯巴比妥或甲喹酮之间协同作用的存在及其机制。对于所有三种催眠药,乙醇均可增加催眠持续时间,但每种药物的作用机制不同。亚催眠剂量的乙醇增加了戊巴比妥的分布容积,随后消除分数的降低延长了催眠药的半衰期。乙醇对甲喹酮的分布和消除没有影响,但靶器官出现了敏感性增加,表现为最小有效剂量降低。乙醇也降低了苯巴比妥的最小有效剂量,但除此之外,催眠期过后苯巴比妥的消除速率增加。