Prediction of Tacrolimus Exposure by CYP3A5 Genotype and Exposure of Co-Administered Everolimus in Japanese Renal Transplant Recipients.
Prediction of Tacrolimus Exposure by CYP3A5 Genotype and Exposure of Co-Administered Everolimus in Japanese Renal Transplant Recipients.
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DOI：
10.3390/ijms19030882
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发表时间：
2018-03-16
影响因子：
5.6
通讯作者：
Miura M
中科院分区：
文献类型：
--
作者：
Kagaya H;Niioka T;Saito M;Inoue T;Numakura K;Yamamoto R;Akamine Y;Habuchi T;Satoh S;Miura M
虽然他克莫司和依维莫司通过 CYP3A4/5 具有共同的代谢途径，但在具有 CYP3A5*3/*3 的受体中，他克莫司仅通过 CYP3A4 代谢。本研究的目的是评估如何根据 CYP3A5 基因型和服用两种药物的肾移植患者中依维莫司的 AUC 来预测他克莫司的血药浓度-时间曲线下面积 (AUC)。计算移植后1个月和1年他克莫司和依维莫司的剂量调整AUC（AUC/D）。对于携带 CYP3A5*1 等位基因或 CYP3A5*3/*3 的患者，一个月和一年时，他克莫司和依维莫司的 AUC/D 之间存在显着相关性。在这两个阶段，与 CYP3A5*1 等位基因相比，CYP3A5*3/*3 患者的决定系数较高，回归方程的斜率较大。在移植后 1 年，CYP3A5*3/*3 患者的单剂量他克莫司和依维莫司之间存在良好的相关性（r = 0.794，p < 0.001）。每种 CYP3A5 基因型的他克莫司 AUC0-24/D 的变异性可以根据依维莫司的 AUC0-12/D 进行预测。临床医生或许能够根据两种药物在每种CYP3A5基因型中AUC的关系来综合进行他克莫司和依维莫司的剂量调整。
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.
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影响因子：
6.7
作者：
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通讯作者：
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