INDIVIDUAL DIFFERENCE IN THE EFFECT OF DRUGS IN RELATION TO THE TISSUE CONCENTRATION OF DRUGS

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Abstract
It has been reported that the alteration in the effect of various drugs is often related to the alteration in the rate of drug-metabolism (1-10). For example, the administration of the phenobarbital and various drugs markedly decreased the effects of numerous drugs through increases in the activities of drug-metabolizing enzymes of liver microsomes (1-5). On the other hand, the effects of various drugs were increased in fasted or low protein diet fed rats through decreases in the activities of drug-metabolizing enzymes (6, 7). It has been reported that species and sex differences in the effects of dugs are often related to the difference in the rate of drug metabolisms (1, 8-11). It is well known that there are marked individual differences in the effects of various drugs in animal and clinical experiments. On the other hand, it has been considered that such individual differences may be due to differences in the sensitivity of the target organs. However, there are no direct evidence for supporting such opinion on the basis of the drug level in the target organs. The present study, therefore, is designed to determine whether the individual differences in the effects of pentobarbital and zoxanolamine are correlated to the difference in the sensitivity or in the drug level of the target organ.