Zhao Yi-Chang, Xiao Chen-Lin, Hou Jing-Jing, Li Jia-Kai, Zhang Bi-Kui, Xie Xu-Biao, Fang Chun-Hua, Peng Feng-Hua, Sandaradura Indy, Yan Miao
Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha 410011, China.
International Research Center for Precision Medicine, Transformative Technology and Software Services, Changsha 410011, China.
Pharmaceutics. 2022 Dec 7;14(12):2739. doi: 10.3390/pharmaceutics14122739.
Tacrolimus is an immunosuppressant with a narrow therapeutic window. Tacrolimus exposure increased significantly during voriconazole co-therapy. The magnitude of this interaction is highly variable, but it is hard to predict quantitatively. We conducted a study on 91 kidney transplantation recipients with voriconazole co-therapy. Furthermore, 1701 tacrolimus concentration data were collected. Standard concentration adjusted by tacrolimus daily dose (C/D) and weight-adjusted standard concentration (CDW) increased to 6 times higher during voriconazole co-therapy. C/D and CDW increased with voriconazole concentration. Patients with the genotype of CYP3A5 *3/*3 and CYP2C19 *2/*2 or *2/*3 were more variable at the same voriconazole concentration level. The final prediction model could explain 54.27% of the variation in C/D and 51.11% of the variation in CDW. In conclusion, voriconazole was the main factor causing C/D and CDW variation, and the effect intensity should be quantitative by its concentration. Kidney transplant recipients with CYP3A5 genotype of *3/*3 and CYP2C19 genotype of *2/*2 and *2/*3 should be given more attention during voriconazole co-therapy. The prediction model established in this study may help to reduce the occurrence of rejection.
他克莫司是一种治疗窗狭窄的免疫抑制剂。在伏立康唑联合治疗期间，他克莫司的暴露量显著增加。这种相互作用的程度高度可变，但很难进行定量预测。我们对91例接受伏立康唑联合治疗的肾移植受者进行了一项研究。此外，收集了1701个他克莫司浓度数据。在伏立康唑联合治疗期间，经他克莫司每日剂量调整的标准浓度（C/D）和体重调整后的标准浓度（CDW）增加至6倍之多。C/D和CDW随伏立康唑浓度升高而增加。在相同伏立康唑浓度水平下，携带CYP3A5 *3/*3和CYP2C19 *2/2或2/3基因型的患者变化更大。最终的预测模型可以解释C/D变化的54.27%和CDW变化的51.11%。总之，伏立康唑是导致C/D和CDW变化的主要因素，其效应强度应通过其浓度进行定量。在伏立康唑联合治疗期间，携带CYP3A5基因型3/3和CYP2C19基因型2/2及2/*3的肾移植受者应给予更多关注。本研究建立的预测模型可能有助于减少排斥反应的发生。
