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The pharmacogenetics of calcineurin inhibitors: one step closer toward individualized immunosuppression?

The immunosuppressive drugs cyclosporin (CsA) and tacrolimus (Tac) are widely used to prevent acute rejection following solid-organ transplantation. However, the clinical use of these agents is complicated by their many side effects, a narrow therapeutic index and highly variable pharmacokinetics. The variability in CsA and Tac disposition has been attributed to interindividual differences in the expression of the metabolizing enzymes cytochrome P450 ( CYP) 3A4 and 3A5, and in the expression of the drug transporter P-glycoprotein (encoded by the ABCB1 gene, formerly known as the multidrug resistance 1 gene). Variation in the expression of these genes could in turn be explained by several recently-identified single nucleotide polymorphisms (SNPs). Determination of these SNPs in (future) transplant recipients has the potential to identify individuals who are at risk of under-immunosuppression or the development of adverse drug reactions. Ultimately, genotyping for CYP3A and ABCB1 may lead to further individualization of immunosuppressive drug therapy for the transplanted patient.[1]

References

  1. The pharmacogenetics of calcineurin inhibitors: one step closer toward individualized immunosuppression? Hesselink, D.A., van Gelder, T., van Schaik, R.H. Pharmacogenomics (2005) [Pubmed]
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