Application of Peroxisomal Drug Metabolism Reactions to the Evaluation of Pharmacological and Toxicological Actions of Drugs

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The present study has been performed to apply the reactions of peroxisomal drug metabolism to the evaluation of the pharmacological and toxicological actions of drugs. The results obtained in this study are summarized as follows.1. The characteristics of peroxisomal drug metabolism reactions: It was established that the oxidative chain- shortening of acyl moieties of drugs were done exclusively by peroxisomal beta-oxidation system, being due to the substrate specificities of enzymes related to these reactions.2. Factors affecting the induction of peroxisomal enzymes by drugs: The structure-reaction relationship and species differences as well as the effect of calcium antagonists in related to enzyme induction were examined.3. The screening methods for the determination of peroxisomal enzyme activities: Using cultured rat hepatocytes, a similar effects of drugs to those in in vivo experiments were obtained.4. The pharmacological and toxicological evaluation of the induction of peroxisomal enzymes by drugs: From the results obtained by a long-term experiment on the effects of drugs such as clofibrate, a hypothesis that the oxidative stress caused by the induction of peroxisomal oxidases may be a major process to lead the hepatocarcinogenesis was unlikely to be acceptable.The results in the present study indicate that the determination of peroxisomal drug metabolizing activities is important to provide the information for the evaluation of the pharmacological and toxicological actions of drugs, especially in the cases of peroxisomal proliferators.