METABOLISM OF DRUGS IN OLD RATS (II) METABOLISM IN VIVO AND EFFECT OF DRUGS IN OLD RATS

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Abstract
It is well known that the effects of some drugs in old animals quite differ from those in young animals. For example, Farner and Verzar (1) observed that the action of amphetamine to increase moter activity was more marked in young rats than in old rats and the action of hexobarbital to antagonized against the amphetamine action was more effective in old rats than in young rats. Moreover, the duration of hexobarbital anesthesia was longer in old rats than in young rats (2). Similarly, Petty and Karler (3) observed that anticonvulsive activity of acetazolamide and phenobarbital was more marked in old rats than in young rats. However, there is no study on the mechanism of such altered drug response in relation to the rate of drug metabolism. In a previous paper it was reported from our laboratory that the activities in the oxidation and reduction of drugs and NADPH-linked electron transport system in liver microsomes of male and female rats were progressively decreased with aging (4). It is, therefore, of interest to investigate whether or not the metabolism in vivo of various drugs is decreased in old rats in accordance with the decrease in the metabolic activities of liver microsomes observed in the in vitro experiments. Moreover, the relationship between the effects of drugs and the rate of in vivo metabolism of drugs in the old rats was studied.