Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University.
Department of Pharmacy, Kyushu University Hospital.
Biol Pharm Bull. 2020;43(10):1600-1603. doi: 10.1248/bpb.b20-00361.
Vonoprazan fumarate (vonoprazan) is a new kind of acid suppressant with potent acid inhibitory effects. Therefore, it has been administered to kidney transplant recipients for treatment or prophylaxis of steroid ulcers, refractory peptic ulcers, and gastroesophageal reflux disease. Because tacrolimus, which is a well-established immunosuppressant for kidney transplantation, and vonoprazan share the CYP3A4 system for metabolism, drug interactions are anticipated upon simultaneous administration. We retrospectively analyzed 52 kidney transplant recipients who were converted from rabeprazole, which has a small effect on the tacrolimus trough blood concentration (C), to vonoprazan between August 2016 and July 2019. We compared the tacrolimus C/tacrolimus dose (C/D) before and after conversion and serum liver enzymes, serum total bilirubin, and the estimated glomerular filtration rate (eGFR). As a result, mean tacrolimus C/D before and after conversion was 1.98 ± 1.02 and 2.19 ± 1.15 (ng/mL)/(mg/d), respectively, (p < 0.001). Additionally, mean aspartate transaminase (AST) before and after conversion was 18.6 ± 4.2 and 19.6 ± 5.2 IU/L, respectively, (p = 0.037). Mean alanine transaminase (ALT) before and after conversion was 15.8 ± 5.5 and 17.6 ± 7.1 IU/L, respectively, (p = 0.007). Mean eGFR before and after conversion was 50.6 ± 14.4 and 51.4 ± 14.7 mL/min/1.73 m, respectively (p = 0.021). Mean AST, ALT, and eGFR were slightly but significantly elevated within normal ranges after conversion. In conclusion, our study suggests that the mean tacrolimus C/D was elevated significantly by converting from rabeprazole to vonoprazan, but it had little clinical significance. Vonoprazan can be administered safely to kidney transplant recipients receiving tacrolimus.
富马酸伏诺拉生(vonoprazan)是一种新型抑酸剂,具有强大的抑酸作用。因此,它已被用于治疗或预防肾移植受者的类固醇溃疡、难治性消化性溃疡和胃食管反流病。由于他克莫司是肾移植的一种成熟的免疫抑制剂,而伏诺拉生的代谢途径与 CYP3A4 系统共享,因此预计同时给药会产生药物相互作用。我们回顾性分析了 52 例肾移植受者,他们在 2016 年 8 月至 2019 年 7 月期间从对他克莫司血药浓度(C)影响较小的雷贝拉唑转换为伏诺拉生。我们比较了转换前后的他克莫司 C/他克莫司剂量(C/D)以及血清肝酶、血清总胆红素和估计肾小球滤过率(eGFR)。结果,转换前后的平均他克莫司 C/D 分别为 1.98±1.02 和 2.19±1.15(ng/mL)/(mg/d),(p<0.001)。此外,转换前后的平均天冬氨酸转氨酶(AST)分别为 18.6±4.2 和 19.6±5.2IU/L,(p=0.037)。转换前后的平均丙氨酸转氨酶(ALT)分别为 15.8±5.5 和 17.6±7.1IU/L,(p=0.007)。转换前后的平均 eGFR 分别为 50.6±14.4 和 51.4±14.7mL/min/1.73m,(p=0.021)。转换后,AST、ALT 和 eGFR 在正常范围内略有但显著升高。总之,我们的研究表明,从雷贝拉唑转换为伏诺拉生后,平均他克莫司 C/D 显著升高,但具有临床意义不大。伏诺拉生可安全用于接受他克莫司治疗的肾移植受者。