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While tacrolimus and everolimus have common metabolic pathways through CYP3A4/5, tacrolimus is metabolized solely by CYP3A4 in recipients with the CYP3A5*3 / *3 . The purpose of this study was to evaluate how the area under the blood concentration-time curves (AUC) of tacrolimus could be predicted based on CYP3A5 genotype and the AUC of everolimus in renal transplant patients taking both drugs. The dose-adjusted AUC (AUC/D) of tacrolimus and everolimus were calculated at one month and one year after transplantation. Significant correlations between the AUC/D of tacrolimus and everolimus were found for patients with the CYP3A5*1 allele or CYP3A5*3 / *3 at both one month and one year. At both stages, the determination coefficients were higher and the slopes of regression equations were larger for patients with CYP3A5*3 / *3 compared to the CYP3A5*1 allele. A good correlation between single doses of tacrolimus and everolimus was found for CYP3A5*3 / *3 patients at 1 year after transplantation ( r = 0.794, p &lt; 0.001). The variability of the AUC 0-24 /D of tacrolimus for each CYP3A5 genotype could be predicted based on the AUC 0-12 /D of everolimus. Clinicians may be able to comprehensively carry out the dose adjustments of tacrolimus and everolimus based on relationship with AUCs of both drugs in each CYP3A5 genotype.

Prediction of Tacrolimus Exposure by CYP3A5 Genotype and Exposure of Co-Administered Everolimus in Japanese Renal Transplant Recipients