CZECH MEDICAL ASSOCIATION J. Ev. PURKYNĚ | |
Journals - Article | |
Česky / Czech version | Čes. slov. Farm., 2007; 56, 220–224 |
Cytochrome P450 3A polymorphism and its importance in cyclosporine and tacrolimus
therapy in transplanted patients ĎURICOVÁ J., GRUNDMANN M. Ostravská univerzita, Zdravotně-sociální fakulta, Ústav klinické farmakologie FN, Ostrava |
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Summary: The calcineurin inhibitors cyclosporine (CsA) and tacrolimus (Tac) are widely used in the
prevention of acute rejection after solid organ transplantation. However, their clinical use is
associated with many adverse reactions. The calcineurin inhibitors CsA and Tac have a narrow
therapeutic index and show highly variable pharmacokinetics. The low CsA and Tac bioavailability
has been attributed to interindividual differences in the expression of the metabolizing enzyme
cytochrome P450 3A. The genes for CYP3A4 and 3A5 undergo genetic polymorphism. The results
of many studies focusing on the impact of CYP 3A polymorphism on CsA and Tac
pharmacokinetics are clear with Tac, where an association between CYP 3A polymorphism and the
pharmacokinetic consequences has been shown. However, the results with CsA are controversial
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