Center for Drug Development Science, Department of Biopharmaceutical Sciences, School of Pharmacy, University of California, San Francisco, CA, USA.
Pharmacol Ther. 2010 May;126(2):146-58. doi: 10.1016/j.pharmthera.2010.01.007. Epub 2010 Feb 11.
The use of the immunosuppressants has revolutionized organ transplantation, including pediatric heart transplantation (PHTx). Recent evidence has shown that pharmacogenomics holds the promise to maximize the likelihood of drug safety and efficacy after the drug and dose are tailored individually based on the translation of pharmacogenomics to patient care. In this review, the immunosuppressants used for the PHTx are introduced, including their similarities and differences in immunosuppressive mechanisms of action, and their unique clinical efficacy and safety issues in relation to genetic polymorphisms in the genes that encode drug-metabolizing enzymes, drug transporters and drug targets. In addition, genetic susceptibility to severe drug-associated complications and strategies for their prevention and treatment are discussed. Moreover, clinically important drug-drug, drug-herb, or drug-food interactions and the effects of demographic and clinical covariates of recipients and donors on clinical endpoints of the PHTx are summarized, respectively. All relevant data are focused mainly on the PHTx. Information provided in this review would be useful for pediatric patient care, in particular for personalized medication, because each and every valuable piece could be fitted to the big picture of how organ rejection would be delayed and even avoided after personalized immunosuppressive therapy.
免疫抑制剂的使用彻底改变了器官移植，包括儿科心脏移植（PHTx）。最近的证据表明，药物基因组学有望在根据药物基因组学将药物和剂量个体化以最大程度地提高药物安全性和疗效后实现个体化。在这篇综述中，介绍了用于 PHTx 的免疫抑制剂，包括它们在免疫抑制作用机制方面的异同，以及与编码药物代谢酶、药物转运体和药物靶点的基因中的遗传多态性相关的独特临床疗效和安全性问题。此外，还讨论了对严重药物相关并发症的遗传易感性及其预防和治疗策略。此外，还分别总结了临床重要的药物-药物、药物-草药或药物-食物相互作用以及受者和供者的人口统计学和临床协变量对 PHTx 临床终点的影响。所有相关数据主要集中在 PHTx 上。本综述提供的信息对儿科患者护理特别有用，尤其是对个性化药物治疗，因为每一个有价值的信息都可以适应个体化免疫抑制治疗后如何延迟甚至避免器官排斥的大局。
