基因多态性对实体器官移植钙神经蛋白抑制剂处置的影响

Effect of genetic polymorphism on disposition of calcineurin inhibitors in solid organ transplantation

钙神经蛋白抑制剂(calcineurin inhibitors,CNIs)他克莫司(tacrolimus,FK506)和环孢素(cyclosporine A,CsA)是目前广泛应用于器官移植术后的2种基础免疫抑制剂,具有治疗指数窄,药物代谢动力学个体差异大的特点。如何根据患者个体差异来制定FK506和CsA的个体化治疗方案,使其疗效达到最佳而毒副作用降至最低,是临床工作者所面临的一大难题。遗传药理学和药物基因组学通过研究编码药物代谢酶、药物转运体以及药物靶分子相关基因的单核苷酸多态性(single nucleotide polymor-phisms,SNPs)对CNIs处置的影响,为免疫抑制剂的个体化治疗提供了一条有益的临床途径。

Calcineurin inhibitors,tacrolimus and cyclosporine,characterized by a narrow therapeutic index and a high variability in pharmacokinetic behaviors,are 2 basic immunosuppressive drugs widely used in solid organ transplantation.Tailoring of immunosuppressive drug therapy to the specific requirements of individual patients to optimize the efficacy and minimize the toxicity remains one of the biggest challenges for doctors in solid organ transplantation.Pharmacogenetic and pharmacogenomic researches,studying the effect of genetic polymorphism encoding drug metabolizing enzymes,drug transporters and pharmacological target molecules on drug disposition and action,hold promise to produce useful clinical tools for individualizing immunosuppressive therapy.