Cytochrome P450 3A polymorphisms and immunosuppressive drugs.
With the use of powerful immunosuppressive drugs, organ transplantation has become the treatment of choice for many cases of end-stage chronic organ failure. The calcineurin inhibitors, cyclosporine and tacrolimus, which are the backbone of current immunosuppressive regimens, may be difficult to use because of the large interindividual variability of their pharmacokinetic characteristics and a narrow therapeutic index. Since cytochrome P450 (CYP) 3A4 and CYP3A5 are both involved in their metabolism, the consequences of the polymorphism of these enzymes were studied. It has been recently shown that the CYP3A5*3 polymorphism is associated with both the pharmacokinetics and pharmacodynamic consequences of tacrolimus. The association between the CYP3A4 and CYP3A5 polymorphisms and cyclosporine pharmacokinetics is more questionable. It is important to test these initial results prospectively to improve the individualized use of these drugs.
Thervet
Eric
E
Hôpital Necker, Service de Transplantation Rénale, 149 rue de Sèvres, 75015 Paris, France. eric.thervet@nck.ap-hop-paris.fr
Legendre
Christopher
C
Beaune
Philippe
P
Anglicheau
Dany
D
D000818:Animals; D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism; D006084:Graft Rejection / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016377:Organ Transplantation / Q000639:trends; D011110:Polymorphism, Genetic / Q000235:genetics*
D007166:Immunosuppressive Agents; D051544:Cytochrome P-450 CYP3A