[Recents advances in the pharmacology of immunosuppressive drugs used in organ transplantation].
Individualization of immunosuppressive drugs may be helped by the use of therapeutic drug monitoring determining the best unique time point for concentration to be controlled or using limited sample strategy to perform abbreviated area under the curve (AUC). Pharmacogenetic analyzes the role of enzymes genetic polymorphisms on pharmacokinetic characteristics. Recent studies have demonstrated that cyclosporine concentration obtained 2 hours after oral intake is the best single point. However, a recent analysis of published data did not sustain the clinical benefit of this approach. Regarding mycophenolate mofetil, the targeted AUC has been defined between 30 and 60 mg/h/l. Clinical results are contradictory and it is not possible for the time being to give a clear answer to its clinical relevance. For tacrolimus, it has been demonstrated that the daily dose needed to achieve adequate trough levels are correlated with cytochrome P450 3A5 expression and therefore the presence of *1 allele. A prospective study has been conducted to demonstrate the clinical consequences of this pharmacogenetic approach.
Thervet
Eric
E
Service de Transplantation et de Soins intensifs, Hôpital Necker, 149, rue de Sèvres, 75015 Paris, France. eric.thervet@nck.aphp.fr
D016572:Cyclosporine / Q000627:therapeutic use; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D016377:Organ Transplantation; D014181:Transplantation Immunology
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid