Drug-Drug Interaction between Tacrolimus and Vonoprazan in Kidney Transplant Recipients.
Drug-Drug Interaction between Tacrolimus and Vonoprazan in Kidney Transplant Recipients.
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DOI：
10.3390/jcm10173964
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发表时间：
2021-08-31
影响因子：
3.9
通讯作者：
Homma M
中科院分区：
文献类型：
--
作者：
Suzuki Y;Yoshihashi T;Takahashi K;Furuya K;Ohkohchi N;Oda T;Homma M
接受他克莫司免疫抑制治疗的肾移植受者通常使用质子泵抑制剂（PPIs）来预防胃溃疡并发症。Vonoprazan是一种钾竞争性酸阻滞剂，是一种新型PPI，与传统PPI（如奥美拉唑、兰索拉唑和雷贝拉唑）具有不同的代谢途径。然而，在移植后初期将传统PPI雷贝拉唑改为沃诺哌赞后，他克莫司血药浓度的变化尚无数据。这是一项对18名肾移植受者的回顾性研究。比较雷贝拉唑改用伏诺哌赞前后他克莫司血药浓度及浓度剂量比。研究了CYP2C19和CYP3A5基因多态性对药物-药物相互作用的影响。他克莫司的波谷浓度中位数（范围）由雷别拉唑切换为沃诺哌嗪后，从5.2（3.6-7.4）增加到8.1 (6.1-11.7)ng/mL （p < 0.0005）。他克莫司C/D比值也由38.1（16.5-138.1）显著升高至48.9 (26.2-207.2)（p < 0.0005）。他克莫司浓度和C/D变化百分比分别为65.8%和41.8%。CYP2C19和CYP3A5基因多态性不影响他克莫司浓度和C/D比的变化。本研究表明，与CYP2C19或CYP3A5基因多态性无关，vonoprazan共给药可增加他克莫司浓度。因此，在移植后早期将伏诺哌赞作为强化胃酸阻滞剂使用时，需要频繁监测血液中他克莫司的浓度。
Kidney transplant recipients with tacrolimus-based immunosuppressive therapy are often treated with proton-pump inhibitors (PPIs) to prevent gastric ulcer complications. Vonoprazan, a potassium-competitive acid blocker, is a novel PPI possessing different metabolic pathways from conventional PPIs (e.g., omeprazole, lansoprazole and rabeprazole). However, no data are available on the change in blood concentration of tacrolimus after switching rabeprazole, a conventional PPI, to vonoprazan coadministration in the initial period of post-transplantation. This is a retrospective study of 18 kidney transplant recipients. The blood concentration and the concentration to dose (C/D) ratio of tacrolimus were compared before and after switching from rabeprazole to vonoprazan. Impacts of CYP2C19 and CYP3A5 genetic polymorphisms on the drug–drug interaction were also examined. The median (range) trough concentration of tacrolimus was significantly increased from 5.2 (3.6–7.4) to 8.1 (6.1–11.7) ng/mL (p < 0.0005) after switching from rabeprazole to vonoprazan. The C/D ratio of tacrolimus was also significantly increased from 38.1 (16.5–138.1) to 48.9 (26.2–207.2) (p < 0.0005). The percent changes of tacrolimus concentrations and C/D were 65.8% and 41.8%, respectively. CYP2C19 and CYP3A5 genetic polymorphisms did not affect the change in concentration and C/D ratio of tacrolimus. The present study indicates that vonoprazan coadministration increases the tacrolimus concentration regardless of CYP2C19 or CYP3A5 genetic polymorphisms. Thus, frequent monitoring of blood tacrolimus concentration is required when vonoprazan is introduced as an intensive gastric acid blocker in the early phase of post-transplantation.
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DOI：
10.1248/yakushi.127.209
发表时间：
2007-01-01
影响因子：
0.3
作者：
Niwa, Toshiro;Yamamoto, Sachiko;Takagi, Akira
通讯作者：
Takagi, Akira
影响因子：
2.1
作者：
Takahashi, Kazushige;Yano, Ikuko;Inui, Ken-ichi
通讯作者：
Inui, Ken-ichi
影响因子：
3.3
作者：
Itagaki, F;Homma, M;Kohda, Y
通讯作者：
Kohda, Y
影响因子：
2.1
作者：
Logan, AJ;Morris-Stiff, GJ;Jurewicz, WA
通讯作者：
Jurewicz, WA
影响因子：
2
作者：
Itagaki, F;Homma, M;Kohda, Y
通讯作者：
Kohda, Y