Effects of genetic polymorphism of drug-metabolizing enzymes on the plasma concentrations of antiepileptic drugs in Chinese population

药物代谢酶基因多态性对中国人群抗癫痫药物血浆浓度的影响

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Abstract

As a chronic brain disease, epilepsy affects ~50 million people worldwide. The traditional antiepileptic drugs (AEDs) are widely applied but showing various problems. Although the new AEDs have partially solved the problems of traditional AEDs, the current clinical application of traditional AEDs are not completely replaced by new drugs, particularly due to the large individual differences in drug plasma concentrations and narrow therapeutic windows among patients. Therefore, it is still clinically important to continue to treat patients using traditional AEDs with individualized therapeutic plans. To date, our understanding of the molecular and genetic mechanisms regulating plasma concentrations of AEDs has advanced rapidly, expanding the knowledge on the effects of genetic polymorphisms of genes encoding drug-metabolizing enzymes on the plasma concentrations of AEDs. It is increasingly imperative to summarize and conceptualize the clinical significance of recent studies on individualized therapeutic regimens. In this review, we extensively summarize the critical effects of genetic polymorphisms of genes encoding drug-metabolizing enzymes on the plasma concentrations of several commonly used AEDs as well as the clinical significance of testing genotypes related to drug metabolism on individualized drug dosage. Our review provides solid experimental evidence and clinical guidance for the therapeutic applications of these AEDs.

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