Personalized immunosuppressive therapy in pediatric heart transplantation: Progress, pitfalls and promises.
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.
Xie
Hong-Guang
HG
Center for Drug Development Science, Department of Biopharmaceutical Sciences, School of Pharmacy, University of California, San Francisco, CA, USA. hongg.xie@gmail.com
D002648:Child; D004347:Drug Interactions; D016027:Heart Transplantation; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods* / Q000639:trends; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D010597:Pharmacogenetics; D057285:Precision Medicine / Q000379:methods* / Q000639:trends; D014181:Transplantation Immunology
D007166:Immunosuppressive Agents