Watari Shogo, Araki Motoo, Matsumoto Jun, Yoshinaga Kasumi, Sekito Takanori, Maruyama Yuki, Mitsui Yosuke, Sadahira Takuya, Kubota Risa, Nishimura Shingo, Wada Koichiro, Kobayashi Yasuyuki, Takeuchi Hidemi, Tanabe Katsuyuki, Kitagawa Masashi, Morinaga Hiroshi, Kitamura Shinji, Sugiyama Hitoshi, Ariyoshi Noritaka, Wada Jun, Watanabe Masami, Watanabe Toyohiko, Nasu Yasutomo
Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
Department of Urology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
Drug Metab Pharmacokinet. 2021 Oct;40:100407. doi: 10.1016/j.dmpk.2021.100407. Epub 2021 May 29.
We evaluated the impact of vonoprazan on blood concentrations of tacrolimus via a retrospective analysis of 52 renal transplant recipients who took tacrolimus and converted from rabeprazole to vonoprazan between August 2018 and September 2019. We compared tacrolimus trough levels upon conversion among groups that were classified based on cytochrome P450 (CYP) gene polymorphisms. CYP3A5 groups were heterozygous or homozygous for CYP3A5∗1 and CYP3A5∗3 alleles. CYP2C19 genotypes were classified as extensive (∗1/∗1), intermediate (∗1/∗2 and ∗1/∗3) or poor metabolizers (∗2/∗2, ∗2/∗3 and ∗3/∗3). Tacrolimus trough levels increased only 0.3 ng/mL upon conversion in the CYP3A5∗3/∗3 group: 5.8 [3.4-7.2] vs 6.1 [3.8-7.9]; p = 0.06. No statistically significance changes in tacrolimus levels also occurred in the CYP3A5∗1/∗1 or CYP3A5∗1/∗3 groups. Subgroup analyses of CYP3A5∗3/∗3 demonstrated low changes for all three CYP2C19 subgroups: 5.2 [4.3-6.5] vs 6.2 [4.3-7.9]; p = 0.07, 6.1 [3.4-7.2] vs 6.7 [4.6-7.9]; p = 0.12 and 5.4 [3.6-6.5] vs 4.7 [3.8-6.3]; p = 1.00, respectively. Conversion to vonoprazan thus resulted in little increase of tacrolimus trough levels, even in the group predicted to be most susceptible (CYP3A5∗3/∗3 and 2C19∗1/∗1), thus supporting the safety of concomitant use of vonoprazan with tacrolimus.
我们通过对52名肾移植受者进行回顾性分析，评估了沃克拉唑对他克莫司血药浓度的影响。这些受者在2018年8月至2019年9月期间服用他克莫司，并从雷贝拉唑转换为沃克拉唑。我们比较了根据细胞色素P450（CYP）基因多态性分类的各组转换时的他克莫司谷浓度。CYP3A5组为CYP3A5∗1和CYP3A5∗3等位基因的杂合子或纯合子。CYP2C19基因型分为广泛代谢型（∗1/∗1）、中间代谢型（∗1/∗2和∗1/∗3）或慢代谢型（∗2/∗2、∗2/∗3和∗3/∗3）。在CYP3A5∗3/∗3组中，转换时他克莫司谷浓度仅增加0.3 ng/mL：5.8 [3.4 - 7.2] vs 6.1 [3.8 - 7.9]；p = 0.06。在CYP3A5∗1/∗1或CYP3A5∗1/∗3组中，他克莫司水平也未发生统计学上的显著变化。对CYP3A5∗3/∗3的亚组分析显示，所有三个CYP2C19亚组的变化都很小：5.2 [4.3 - 6.5] vs 6.2 [4.3 - 7.9]；p = 0.07，6.1 [3.4 - 7.2] vs 6.7 [4.6 - 7.9]；p = 0.12，以及5.4 [3.6 - 6.5] vs 4.7 [3.8 - 6.3]；p = 1.00。因此，即使在预计最易受影响的组（CYP3A5∗3/∗3和2C19∗1/∗1）中，转换为沃克拉唑后他克莫司谷浓度也几乎没有增加，从而支持了沃克拉唑与他克莫司联合使用的安全性。
