四种药物毒性的昼夜节律变化

本文依据时间药理学的原理和方法,对抗肿瘤药苦参总碱、皮质激素类药氢化可的松、强心药洋地黄毒甙和镇静催眠药戊巴比妥钠对小白鼠的急性毒性进行测定。结果表明,四种药物 LD_(50)值具有明显的昼夜节律变化,均依照一天中的时辰呈现一定的数学函数曲线。每种药物毒性最强和最低出现的时刻不尽相同,但将其 LD_(50)值进行比较皆有显著性差异。文末对药物毒性昼夜节律变化的原因作了分析,强调时间毒性(chronotoxicity)在药学研究和临床用药中的意义和作用。

CIRCADIAN RHYTHM DEPENDENCY IN ACUTE TOXICITY OF FOUR DRUGS IN MICE

A current interest in pharmacology is evaluating circadian variety of various medicines.This research conducted basic trial on mice looking for evidence of circadian rhythm in the toxic effects.Mice which had been acclimated to a 12- hour light-dark cycle were given matrine alkali,hydrocortisone,digitoxin or sodium pentobarbital at one of 6 different times during 24-hour period.It was found that the LD_(50)values were a function of time of day.The greatest toxicity(mi- nimal LD_(50)value)during 24-hour period was noted at 08:00 h for both matrine alkali and hydrocortisone,but at 24:00 h for digitoxin,at 20:00 h for sodium pentobarbital.The least toxicity(maximum LD_(50)value)occurred at 24:00 h,20: 00 h,I2:00 h or 04:00 h for those drugs according to the order of above.In all cases the differnt between peak and trough value were significant(p<0.05). In addition,under same experimental condition the anesthetized effect of sodium pentobarbital exhibited a circadian variety also.The implications of those findings and the need for standardized conditions during drug toxicity test are discussed.