Department of Gastroenterology and Hepatology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands.
Best Pract Res Clin Gastroenterol. 2012 Feb;26(1):85-95. doi: 10.1016/j.bpg.2012.01.017.
Calcineurin inhibitors (CNIs), such as cyclosporin A and tacrolimus, are the cornerstone of maintenance immunosuppressive regimens in liver transplantation. CNIs prevent rejection by inhibition of calcineurin, via which lymphocyte proliferation and interleukin (IL)-2 production is prevented. Tacrolimus is now the first-choice immunosuppressant after liver transplantation, since it is associated with fewer episodes of rejection than cyclosporin A. In this review we will discuss interindividual differences, which influence tacrolimus metabolism. Because of these factors and the narrow therapeutic index of tacrolimus, monitoring of drug trough levels is necessary. Furthermore, we will discuss studies concerning conversion from the tacrolimus twice daily to tacrolimus once daily formulation in stable LT patients. Due to adverse effects of CNIs, such as chronic renal failure, hypertension, de novo malignancy and new-onset diabetes mellitus, CNI minimization strategies have been developed, which will be discussed too.
钙调磷酸酶抑制剂（CNIs），如环孢素 A 和他克莫司，是肝移植中维持免疫抑制方案的基石。CNIs 通过抑制钙调磷酸酶来预防排斥反应，从而阻止淋巴细胞增殖和白细胞介素（IL）-2 的产生。他克莫司现在是肝移植后的首选免疫抑制剂，因为与环孢素 A 相比，它引起排斥反应的次数更少。在这篇综述中，我们将讨论影响他克莫司代谢的个体差异。由于这些因素和他克莫司的治疗指数狭窄，需要监测药物谷浓度。此外，我们还将讨论关于将稳定的 LT 患者从他克莫司每日两次给药转换为他克莫司每日一次制剂的研究。由于 CNIs 存在不良反应，如慢性肾衰竭、高血压、新发恶性肿瘤和新发糖尿病，因此开发了 CNIs 最小化策略，我们也将对此进行讨论。
