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

International Journal of Molecular Sciences

Shigeru Satoh¹  Yumiko Akamine²  Masatomo Miura²  Takenori Niioka²  Hideaki Kagaya²  Takamitsu Inoue³  Mitsuru Saito³  Tomonori Habuchi³  Ryohei Yamamoto³  Kazuyuki Numakura³ 

[1] Center for Kidney Disease and Transplantation, Akita University Hospital, 1-1-1 Hondo, Akita 010-8543, Japan;Department of Pharmacy, Akita University Hospital, 1-1-1 Hondo, Akita 010-8543, Japan;Department of Urology, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan;

关键词: tacrolimus;    everolimus;    CYP3A5 polymorphism;    renal transplantation;   

DOI  :  10.3390/ijms19030882

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown