Journal
PHARMACOGENOMICS
Volume 6, Issue 1, Pages 37-47Publisher
FUTURE MEDICINE LTD
DOI: 10.1517/14622416.6.1.37
Keywords
cyclosporine; CYP3A4; CYP3A5; cytochrome P450; organ transplantation; pharmacogenetics; SNP; tacrolimus
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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.
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