Pharmacogenetics of drug-metabolizing enzymes: implications for a safer and more effective drug therapy
Pharmacogenetics of drug-metabolizing enzymes: implications for a safer and more effective drug therapy
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DOI：
10.1098/rstb.2005.1685
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发表时间：
2005-08-22
影响因子：
6.3
通讯作者：
Rodriguez-Antona, C
中科院分区：
文献类型：
--
作者：
Ingelman-Sundberg, M;Rodriguez-Antona, C
大多数I相和II相依赖性药物代谢是由多态性酶进行的，多态性酶可导致药物代谢的消除、定量或定性降低或增强。存在几个实例，其中携带某些等位基因的受试者由于由多个基因或通过诱导基因表达引起的超速代谢而不能从药物治疗中受益，或者，由于存在缺陷等位基因而遭受药物治疗的不良作用。很可能，未来对这些酶的预测性基因分型可能使15-25%的药物治疗受益，从而预防药物不良反应和因果关系，从而改善相当一部分患者的健康。然而，这将需要一段时间才能在诊所内成为现实。我们描述了该领域的一些重要方面，重点是细胞色素P450，并讨论了CYP 3A 5和CYP 3A 7的胎儿表达的多态性方面。
The majority of phase I- and phase II-dependent drug metabolism is carried out by polymorphic enzymes which can cause abolished, quantitatively or qualitatively decreased or enhanced drug metabolism. Several examples exist where subjects carrying certain alleles do not benefit from drug therapy due to ultrarapid metabolism caused by multiple genes or by induction of gene expression or, alternatively, suffer from adverse effects of the drug treatment due to the presence of defective alleles. It is likely that future predictive genotyping for such enzymes might benefit 15-25% of drug treatments, and thereby allow prevention of adverse drug reactions and causalities, and thus improve the health of a significant fraction of the patients. However, it will take time before this will be a reality within the clinic. We describe some important aspects in the field with emphasis on cytochrome P450 and discuss also polymorphic aspects of foetal expression of CYP3A5 and CYP3A7.