Short communication: switching immunosuppression from cyclosporine to tacrolimus in kidney transplant recipients based on CYP3A5 genotyping.

BACKGROUND: Kidney transplant recipients on long-term cyclosporine (CsA) therapy may develop multiple adverse drug events, and immunosuppression conversion from CsA to tacrolimus (Tac) is an option. Genetic variations, especially cytochrome P450 (CYP) 3A5*3 affects Tac dosing. However, little information is available to guide the conversion with regards to patients' pharmacogenomics. We aimed to investigate whether CYP3A5, CYP3A4 and ABCB1 genotyping could contribute to a more precise and individualized initial dosing of Tac at the time of immunosuppressant conversion.

METHODS: Genotypes of 5 candidate genes (CYP3A5*3, CYP3A4*1G, ABCB1C1236T, ABCB1C3435T, ABCB1G2677T/A) were investigated by polymerase chain reaction and restriction fragment-length polymorphism methods in 46 adult kidney transplant recipients requiring immunosuppressant conversion from CsA to TAC. Associations between these functional genetic polymorphisms and the dose-adjusted trough concentrations of CsA and Tac were evaluated, retrospectively.

RESULTS: Based on the linear regression analysis, CYP3A5 expressers (*1/*1 and *1/*3) had lower Tac dose-adjusted trough concentrations on days 7, 14, 21 and 28, and they required 1.40- to 1.75-fold higher daily dose to reach the target concentration compared to non-expressers (*3/*3) on day 28 [0.07 (0.06-0.09) mg/kg/day vs 0.05 (0.02-0.06) mg/kg/day, P=0.001]. CYP3A4*1G or ABCB1 genetic polymorphisms had no effect on the Tac dose-adjusted trough concentrations.

CONCLUSION: Our preliminary study supports the use of CYP3A5 genotyping to guide the initial dosing of Tac when converting the immunosuppression therapy from CsA to Tac.