多药物联合作用的评价及计算机分析

当合并药的对数剂量-概率单位直线不相平行时,药物联合作用的性质常与反应水平有关。应用Finney或Loewe的合并指标Q_50只能决定质反应率在50％时的联合作用,不能推及其他反应水平。本文提出更一般性的多药物合并指标Q(x)及95％可信限,对任何反应水平适用。应用计算机程序,可使Q(x)分析十分简便。 本文用两个实例:氯哌酰胺合并前列腺素F_2a口对大鼠的抗早孕试验,以及3个硝基甲苯类化合物对小鼠的联合毒性试验,以说明药物联合作用的计算机分析的可行性。

AN EVALUATION OF MULTI-DRUG COMBINATION AND THE COMPUTER ANALYSIS

The effects of a combination of drugs are dependent on the levels of reactions to the drugs when the logdose-probit lines of drugs combined are not parallel. The combination index, Q50, used by Finney and Loewe's methods only indicates the combination effect of a 50% quantal response. A method which can be applied more generally to any number of drugs combined and at any reactive level is to use Q(x) in place of Q50, where (x) is an arbitrary effect level. A formula for calculating the 95% confidence limits of Q(x) is also proposed.Computer programs for the above analyses have been developed for IBM-PC series. This automated method has been used by the author for analysis of two pharmacological studies, i. e. the joint action of loperamide and PGP2a for terminating early pregnancy in rats, and the combined toxicity of nitro-oompounds in mice. These two examples illustrate the validity of the procedure, and shows it to be more convenient and generally applicable.