Audie Murphy VA Medical Center, San Antonio, TX, USA.
Division of Cardiology, Department of Medicine, Joe R. and Teresa Long School of Medicine, University of Texas Health San Antonio, San Antonio, TX, USA.
Handb Exp Pharmacol. 2022;272:27-38. doi: 10.1007/164_2021_549.
Calcineurin inhibitors (CNIs) have been the foundation of immunosuppression in solid organ transplantation since the 1980s. Cyclosporine A (CSA), the first in class, was identified as the metabolite of the soil fungus Tolypocladium inflatum Gams as part of a larger program of screening for naturally occurring fungal metabolites with biologic activity in the 1970s. Significant immunosuppressive effects were discovered and consequently CSA was trialed as an immunosuppressant in renal transplantation. This initial success led to its widespread study and adoption in solid organ transplantation. This novel agent yielded significant improvements in both 1 year and longer-term allograft and patient survival. Subsequently, a similar and more potent CNI, tacrolimus was developed. Today, it is the principal CNI used for prevention of allograft rejection. Like all other immunosuppressives, the benefits of CNIs are counterbalanced by side effects and complications resulting from drug toxicity. This chapter comprehensively reviews the clinical use of CNIs in cardiac transplantation.
钙调磷酸酶抑制剂（CNIs）自 20 世纪 80 年代以来一直是实体器官移植中免疫抑制的基础。环孢素 A（CSA）作为第一个同类药物，是在 20 世纪 70 年代更大规模的筛选具有生物活性的天然真菌代谢产物的计划中，被鉴定为土壤真菌 Tolypocladium inflatum Gams 的代谢产物。发现了其具有显著的免疫抑制作用，因此 CSA 被试用作为肾移植中的免疫抑制剂。这一初步成功促使 CSA 在实体器官移植中广泛研究和采用。这种新型药物在 1 年和长期移植物和患者存活率方面都取得了显著的改善。随后，开发了类似的、更有效的 CNI 他克莫司。如今，它是预防移植物排斥反应的主要 CNI。与所有其他免疫抑制剂一样，CNIs 的益处因药物毒性引起的副作用和并发症而受到平衡。本章全面回顾了 CNI 在心脏移植中的临床应用。
