ヒト肝チトクロムP-450の遺伝的変動と臨床薬物動態論

概要

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Cytochrome P-450 is the collective term for a group of isozymes which are responsible for the oxidative metabolism of numerous drugs and xenobiotica. There is a large difference in the metabolic potency of P-450 to oxidize several drugs such as debrisoquine and mephenytoin. In recent years it was elusidated to be attributed to genetic polymorphism of cytochrome P-450. The plasma concentration of poor metabolizers after administration of usual dosage rise relatively high and occationaly develop toxic level. So genetic polymorphism is of significance in patient management for those drugs for which therapeutic index is small and therapeutic drug level monitoring is considered useful. The increasing knowledge of specific substrates and inhibitors of individual P-450 isozymes makes it possible to predict competitive drug-drug interactions. In this review, we summalize the characteristics of cytochrome P-450 isozymes and discuss clinical significance of genetic polymorphism of cytochrome P-450 and mechanism of drug-drug interactions.
日本医療薬学会の論文
1992-12-21