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

• Main Authors: Hideaki Kagaya, Takenori Niioka, Mitsuru Saito, Takamitsu Inoue, Kazuyuki Numakura, Ryohei Yamamoto, Yumiko Akamine, Tomonori Habuchi, Shigeru Satoh, Masatomo Miura
• Format: Article
• Language: English
• Published: MDPI AG 2018-03-01
• Series: International Journal of Molecular Sciences
• Subjects: tacrolimus; everolimus; CYP3A5 polymorphism; renal transplantation
• Online Access: http://www.mdpi.com/1422-0067/19/3/882

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 < 0.001). The variability of the AUC0–24/D of tacrolimus for each CYP3A5 genotype could be predicted based on the AUC0–12/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.