Effects of lansoprazole and rabeprazole on tacrolimus blood concentration: Case of a renal transplant recipient with CYP2C19 gene mutation
Effects of lansoprazole and rabeprazole on tacrolimus blood concentration: Case of a renal transplant recipient with CYP2C19 gene mutation
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DOI：
10.1097/00007890-200201270-00028
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发表时间：
2002-01-27
期刊：
影响因子：
6.2
通讯作者：
Kohda, Y
中科院分区：
文献类型：
--
作者：
Homma, M;Itagaki, F;Kohda, Y
当患者同时服用他克莫司和质子泵抑制剂(PPI)兰索拉唑和雷贝拉唑时，它们可能会相互作用于它们的肝脏消除，因为PPIs和他克莫司共享细胞色素P450(CYP)3A4来实现它们的肝脏消除。这种药物相互作用可能在PPI、广泛代谢物和较差代谢物的代谢状态之间观察到不同，这被归类为CYP2C19基因多态(1)。我们报道了兰索拉唑和雷贝拉唑对肾移植患者中他克莫司血药浓度的影响。一名57岁的身体肾移植患者接受了他克莫司、强的松龙和霉酚酸酯的免疫抑制治疗。因消化性溃疡于术后第19天开始服用兰索拉唑(30 mg/d)。他克莫司谷值维持在16.3~17.6 ng/ml，每日剂量22 mg，用兰索拉唑3d后显著升高至26.7 ng/ml。由于其他药物及肝肾功能在应用兰索拉唑前后无明显变化，故认为他克莫司浓度升高是药物与兰索拉唑相互作用所致。在第71天将兰索拉唑改为法莫替丁(40 mg/d)后，他克莫司水平从12.0-15.4 ng/ml下降到8.0 ng/ml，但他克莫司的剂量保持不变(8 mg/d)。第152天开始用雷贝拉唑(10 mg/d)代替法莫替丁，以缓解消化性溃疡复发所产生的症状。在将法莫替丁改为雷贝拉唑之前或之后，血液中他克莫司的水平没有变化。
Tacrolimus and the proton pump inhibitors (PPIs), lansoprazole and rabeprazole, potentially interact on their hepatic elimination when patients take them simultaneously, because the PPIs and tacrolimus share the cytochrome P450 (CYP) 3A4 for their hepatic elimination. This drug interaction may be observed differently between metabolic status of PPIs, extensive and poor metabolizers, which are assigned to CYP2C19 gene polymorphism (1). We report the effects of lansoprazole and rabeprazole on tacrolimus blood concentration in the case of a renal transplant recipient with CYP2C19 gene mutation.A 57-year-old woman who underwent cadaveric renal transplantation received tacrolimus, prednisolone, and mycophenolate mofetil for her immunosuppression. Lansoprazole (30 mg/day) was started on postoperative day 19 because of peptic ulcer. Tacrolimus trough levels maintained at 16.3–17.6 ng/ml with the daily dose of 22 mg drastically increased to 26.7 ng/ml 3 days after introducing lansoprazole. Because other medications and liver and kidney functions did not change before or after introducing lansoprazole, it was considered that the elevation of tacrolimus level was caused by the drug interaction with lansoprazole. Switching lansoprazole to famotidine (40 mg/day) on day 71 produced a decline in tacrolimus levels from 12.0–15.4 ng/ml to 8.0 ng/ml, although the dose of tacrolimus remained unchanged (8 mg/day). On day 152, rabeprazole (10 mg/day) was started instead of famotidine to heal the symptoms generated from the recurrence of peptic ulcer. There was no change in blood tacrolimus levels before or after switching famotidine to rabeprazole.