Role of pharmacogenetics of immunosuppressive drugs in organ transplantation.
The promising role of pharmacogenetics in the attempt to elucidate the inherited basis of differences between individual responses to drugs lies in its potential ability to identify the right drug and dose for each patient. Because immunosuppressive treatments are concentration-critical drugs, therapeutic drug monitoring is mandatory for most of them. After the description of the metabolic pathways of these drugs, the discovery of gene polymorphism has led to the hypothesis that these polymorphisms may be predictive of both pharmacokinetic and pharmacodynamic outcomes after transplantation. In this review, the authors describe the current knowledge regarding gene polymorphisms of metabolizing enzymes and transporters of immunosuppressive drugs. The authors also describe the future development of pharmacogenetics, which could help to better define the correct drug to use, the choice of an adequate initial dose, and the individualization of the risk associated with the use of such drugs after organ transplantation.
Thervet
Eric
E
Service de Transplantation Rénale, Hôpital Necker, Paris, France. ethervet@noos.fr
Anglicheau
Dany
D
Legendre
Christophe
C
Beaune
Philippe
P
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D001379:Azathioprine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D016377:Organ Transplantation; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D020123:Sirolimus / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D001379:Azathioprine; D020123:Sirolimus; D016559:Tacrolimus