Clinical pharmacogenetics of immunosuppressive drugs in organ transplantation.
Organ transplantation has become an important additional option for patients with organ failure. Immunosuppressive drugs showing a very narrow therapeutic window have to be administered. Different transporters and metabolic pathways are responsible for absorption and metabolism of these drugs; for instance, the P-glycoprotein (P-gp) pump regulates the absorption of a drug, and its metabolism is catalyzed by cytochrome P450s (CYPs). As the phenotypes of P-gp or the CYPs are predetermined by their genotypes, genetic testing prior to drug therapy may help to predict the drug doses required. This review describes polymorphisms of the genes coding for P-gp and CYPs, and focuses on the compounds cyclosporin and tacrolimus. It is hoped that this information might help to judge the value of pharmacogenetic testing prior to immunosuppressive therapy in solid organ transplantation.
Szekeres
Thomas
T
Medical University of Vienna, Clinical Institute for Medical and Chemical Laboratory Diagnostics 5H, General Hospital of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. thomas.szekeres@meduniwien.ac.at
Haushofer
Alexander
A
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016377:Organ Transplantation; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003577:Cytochrome P-450 Enzyme System; D016559:Tacrolimus