CYP3A5 Genotype Does Not Influence the Blood Concentration of Tacrolimus Measured with the Abbott Immunoassay

Abstract

Therapeutic drug monitoring of immunosuppressants is well established as an aid to optimizing patient management after allograft transplantation. Most laboratories measure cyclosporin and tacrolimus by immunoassays. However, measured values may be affected by the presence of circulating metabolites because of the limited specificity of the antibodies used in these assays. Cyclosporin is metabolized by the cytochrome P450 3A4 (CYP3A4) and cytochrome P450 3A5 (CYP3A5) enzymes. Studies on the biotransformation of cyclosporin by CYP3A4 and CYP3A5 have demonstrated disparate patterns of metabolite profiles between the 2 enzymes for this substrate. CYP3A4 catalyzes the formation of 3 primary cyclosporin metabolites; 2 are monohydroxylated (AM1 and AM9), and the third is demethylated (AM4N). CYP3A5 produces only the AM9 metabolite (1). This may have important implications for immunoassay measurements of cyclosporin, as polymorphic expression of the CYP3A5 gene leads to some individuals not producing the CYP3A5 …