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

While tacrolimus and everolimus have common metabolic pathways through CYP3A4/5, tacrolimus is metabolized solely by CYP3A4 in recipients with the /. 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 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 allele or / 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 / compared to the allele. A good correlation between single doses of tacrolimus and everolimus was found for / patients at 1 year after transplantation ( = 0.794, < 0.001). The variability of the AUC/D of tacrolimus for each genotype could be predicted based on the AUC/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 genotype.