[Pharmacogenetics and immunosuppressor drugs: impact and clinical interest in transplantation].
The domain of solid organ transplantation is characterized by the use of variable drug combinations with drug-drug interactions, and the presence of two genomes, that of the transplanted organ and that of the receiver, which can be involved in the pharmacogenetics of these drugs. This paper is a literature review of the impact of the genetic polymorphisms of the metabolic enzymes, efflux transporters and therapeutic targets of the main immunosuppressive drugs (cyclosporine, tacrolimus, sirolimus and mycophenolate) on the dose-concentration and concentration-effect relationships of these drugs. The polymorphisms of metabolic enzymes have significant effects on the pharmacokinetics of all these drugs, but the clinical trials for validating treatment individualization based on these genetic differences are still lacking. It should be noted that the influence of the donor's genome has seldom been studied and has been found to be significant in liver transplant recipients. The influence of efflux transporter genes polymorphisms, in particular of P-glycoprotein and MPR2, is controversial. As for the polymorphisms of the drug targets genes, either they have not been reported (calcineurin, mTOR), or their influence has only been the subject of a few preliminary studies (IMPDH2). The pharmacogenetics of immunosuppressants is thus still an open field for investigations and potential therapeutic progress.
Marquet
P
P
Service de Pharmacologie-Toxicologie, CHU Dupuytren, Limoges Cedex, France. pierre.marquet@unilim.fr
Djebli
N
N
Picard
N
N
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004798:Enzymes / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D010597:Pharmacogenetics; D014181:Transplantation Immunology
D002352:Carrier Proteins; D004798:Enzymes; D007166:Immunosuppressive Agents