Delayed effect of grapefruit juice on pharmacokinetics and pharmacodynamics of tacrolimus in a living-donor liver transplant recipient
Delayed effect of grapefruit juice on pharmacokinetics and pharmacodynamics of tacrolimus in a living-donor liver transplant recipient
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DOI：
10.2133/dmpk.21.122
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发表时间：
2006-01-01
影响因子：
2.1
通讯作者：
Inui, Ken-ichi
中科院分区：
文献类型：
--
作者：
Fukatsu, Sachio;Fukudo, Masahide;Inui, Ken-ichi
他克莫司是一种钙调神经磷酸酶抑制剂，已广泛用于预防移植后的同种异体移植排斥。我们报告一例活体肝移植受者在连续 3 天同时摄入 4 次葡萄柚汁 (250 mL) 后，他克莫司的血药谷浓度显着增加。在重复摄入葡萄柚汁期间或之后，他克莫司的血谷浓度没有变化。然而，在最终摄入后近1周，他克莫司的血药浓度从摄入前的4.7 ng/mL显着升高至47.4 ng/mL，导致外周血单核细胞中钙调神经磷酸酶活性显着降低。此外，在血液浓度升高的整个过程中，出现了头痛和恶心，但没有出现肾毒性或高血糖。葡萄柚汁可能对他克莫司的药代动力学和药效学具有临床显着影响。建议接受他克莫司治疗的移植受者避免饮用葡萄柚汁。
Tacrolimus is a calcineurin inhibitor that has been widely used to prevent allograft rejection after transplantation. We report a case of a living-donor liver transplant recipient experiencing a considerable increase in the trough blood concentration of tacrolimus after concomitant ingestion of grapefruit juice (250 mL) 4 times for 3 days. The trough blood concentrations of tacrolimus were not changed during or immediate after the repeated intake of grapefruit juice. However, almost 1 week after the final ingestion, the blood concentration of tacrolimus markedly increased to as much as 47.4 ng/mL from 4.7 ng/mL before the ingestion, resulting in a profound reduction of calcineurin phosphatase activity in peripheral blood mononuclear cells. Furthermore, headache and nausea, but not nephrotoxicity or hyperglycemia, took place throughout the period of the elevated blood concentrations. Grapefruit juice may have a clinically significant effect on the pharmacokinetics and pharmacodynamics of tacrolimus. It is recommended to avoid the consumption of grapefruit juice in transplant recipients treated with tacrolimus.