St. George's, University of London, London, UK.
Ther Drug Monit. 2010 Jun;32(3):261-4. doi: 10.1097/FTD.0b013e3181dca995.
Pharmacogenetic strategies offer promise as an adjunct to therapeutic drug monitoring in achieving target blood concentrations of the immunosuppressive drugs as early as possible after transplantation. To date, the only strategy to have been tested in a clinical trial is the use of the cytochrome P450 3A5 (CYP3A5) genotype to predict tacrolimus dose. Other potential candidates are CYP3A5 and sirolimus and UGT1A9 for mycophenolate. There are also genetic predictors of pharmacodynamics, including IMPDH1 for mycophenolate and ABCB1 for cyclosporine that may identify individuals at particular risk of efficacy failure or toxicity with a given drug. As pharmacogenetic testing moves into routine clinical practice, standards for service delivery and reporting of results need to be established.
遗传药理学策略有望成为治疗药物监测的辅助手段,以在移植后尽早实现免疫抑制药物的目标血药浓度。迄今为止,唯一在临床试验中进行过测试的策略是使用细胞色素 P450 3A5(CYP3A5)基因型来预测他克莫司的剂量。其他潜在的候选药物是 CYP3A5 和西罗莫司以及 UGT1A9 用于霉酚酸酯。还有药效动力学的遗传预测因子,包括霉酚酸酯的 IMPDH1 和环孢素的 ABCB1,它们可能确定特定个体对特定药物的疗效失败或毒性的风险。随着遗传药理学检测进入常规临床实践,需要建立服务提供和结果报告的标准。