Developmental pharmacogenetics of immunosuppressants in pediatric organ transplantation.
Cyclosporine, tacrolimus, sirolimus, and mycophenolate mofetil are the primary immunosuppressants used on pediatric organ transplantation. Therapeutic drug monitoring is used in daily practice, because their clinical use is hampered by a narrow therapeutic index and large variability. Tailoring immunosuppressive therapy to the individual patient to optimize efficacy and minimize toxicity is therefore essential. Because research in pharmacogenetics already identified polymorphisms impacting their pharmacokinetic parameters in adults, developmental pharmacogenetics of immunosuppressants holds promises for optimizing dosage regimens and improving clinical outcome in children. In this review, we focus on the impact of age and pharmacogenetics on these immunosuppressants in children undergoing organ transplantation.
Department of Pediatric Pharmacology and Pharmacogenetics, Clinical Investigation Center (CIC) Inserm 9202, Hôpital Robert Debré, Paris, France.
Wei
W
Zhao
May
M
Fakhoury
Evelyne
E
Jacqz-Aigrain
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000367:Age Factors; D002648:Child; D016572:Cyclosporine / Q000493:pharmacokinetics / Q000627:therapeutic use; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D016903:Drug Monitoring; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D016377:Organ Transplantation; D011110:Polymorphism, Genetic; D020123:Sirolimus / Q000493:pharmacokinetics / Q000627:therapeutic use; D016559:Tacrolimus / Q000493:pharmacokinetics / Q000627:therapeutic use
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D007166:Immunosuppressive Agents; C073119:TAP1 protein, human; D016572:Cyclosporine; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; D014453:Glucuronosyltransferase; D009173:Mycophenolic Acid; D020123:Sirolimus; D016559:Tacrolimus