论文部分内容阅读
硫嘌呤类药物作为一类常用的免疫抑制药,广泛应用于临床。然而其治疗窗窄,药动学个体差异大一直是困扰该类药物临床应用的难题。许多因素可影响硫嘌呤类药物的代谢及药理效应,但其代谢过程中涉及的代谢酶所具有的遗传药理学方面的个体差异被认为是主要因素。近年来各主要代谢酶的遗传多态性对硫嘌呤类药物药动学和药效学的影响也逐渐成为了关注的焦点。因此本文就相关代谢酶(TPMT,ITPA,GST,HPRT,XO,IMPDH及GMPS)的遗传多态性与硫嘌呤类药物疗效和不良反应的相关性进行综述,以期为临床硫嘌呤类药物个体化应用提供指导。
Thiopurines as a common class of immunosuppressive drugs, widely used in clinical. However, its therapeutic window is narrow, large individual differences in pharmacokinetics have been troubling the clinical application of such drugs. Many factors can affect the metabolism and pharmacological effects of the thiopurines, but individual differences in the genetic pharmacology of the metabolic enzymes involved in their metabolism are considered to be the major factors. In recent years, the genetic polymorphism of major metabolic enzymes on the pharmacokinetics and pharmacodynamics of thiopurines has gradually become the focus of attention. Therefore, this review summarizes the relativity between the genetic polymorphisms of the relevant metabolic enzymes (TPMT, ITPA, GST, HPRT, XO, IMPDH and GMPS) and the efficacy and adverse reactions of thiopurines in order to individualize the clinical thiopurines Application guidance.