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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