Miedziaszczyk Miłosz, Karczewski Marek, Idasiak-Piechocka Ilona
Department of General and Transplant Surgery, Poznan University of Medical Sciences, 61-701, Poznan, Poland.
Department of Clinical Pharmacy and Biopharmacy, Poznan University of Medical Sciences, 61-701, Poznan, Poland.
Sci Rep. 2025 Jan 13;15(1):1805. doi: 10.1038/s41598-025-85534-w.
Tacrolimus is metabolized in the liver with the participation of cytochrome P450 isoforms 3A4 and 3A5 (CYP3A4, CYP3A5). Omeprazole, unlike famotidine, is a substrate and inhibitor of CYP2C19, CYP3A4, CYP3A5 enzymes. The aim of the study is to compare the effect of omeprazole and famotidine on the tacrolimus concentration and the kidney transplant function. A randomized study was conducted in 24 adult patients with stable kidney transplant function who received a standard triple immunosuppression regimen. Patients were assigned to the group I (n = 12) additionally receiving omeprazole (20 mg) or the group II (n = 12) receiving famotidine (20 mg). At the time of qualification and during follow-up visits, tacrolimus blood concentration and selected laboratory tests were performed. Statistical analysis was performed using the MedCalc system. The value of tacrolimus concentration in the blood increased after a year in the group I (7.27 ± 2.33 vs 9.20 ± 2.46 ng/mL, p = 0.0478). A reduction in tacrolimus dosage was observed after three years in the group I (3.56 ± 1.75 vs 2.78 ± 1.00 mg, p = 0.0440) and in the group II (2.72 ± 0.84 vs 2.10 ± 0.48 mg, p = 0.0051). There was significant difference in the percentage changes of glomerular filtration rate between the groups after 3 years of the study (- 5.56% vs 9.13%, p = 0.0343). Omeprazole significantly change the concentration of tacrolimus in the blood when administered together with tacrolimus after one year of observation. There was no effect of famotidine or omeprazole on the function of the kidney transplant. ClinicalTrials.gov identifier: NCT05061303.
他克莫司在细胞色素P450同工酶3A4和3A5(CYP3A4、CYP3A5)参与下于肝脏中代谢。与法莫替丁不同,奥美拉唑是CYP2C19、CYP3A4、CYP3A5酶的底物和抑制剂。本研究的目的是比较奥美拉唑和法莫替丁对他克莫司浓度及肾移植功能的影响。对24例接受标准三联免疫抑制方案且肾移植功能稳定的成年患者进行了一项随机研究。患者被分配到额外接受奥美拉唑(20毫克)的I组(n = 12)或接受法莫替丁(20毫克)的II组(n = 12)。在入组时和随访期间,检测了他克莫司血药浓度及选定的实验室检查项目。使用MedCalc系统进行统计分析。I组患者一年后他克莫司血药浓度值升高(7.27±2.33 vs 9.20±2.46纳克/毫升,p = 0.0478)。三年后,I组(3.56±1.75 vs 2.78±1.00毫克,p = 0.0440)和II组(2.72±0.84 vs 2.10±0.48毫克,p = 0.0051)的他克莫司剂量均出现降低。研究三年后,两组间肾小球滤过率的百分比变化存在显著差异(-5.56% vs 9.13%,p = 0.0343)。观察一年后,奥美拉唑与他克莫司合用时显著改变了他克莫司的血药浓度。法莫替丁或奥美拉唑对肾移植功能无影响。ClinicalTrials.gov标识符:NCT05061303。