他克莫司在器官移植中的毒性:综述

A. Sharifi, Azadeh Aminzadeh
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引用次数: 1

摘要

他克莫司是一种大环内酯类抗生素,可作为钙调磷酸酶抑制剂。它被广泛用于防止器官移植排斥反应。已被批准作为器官移植后的一线治疗药物。他克莫司治疗范围窄,药代动力学个体差异大。在器官移植中,免疫抑制与重要风险相关,特别是与感染和心血管疾病相关的风险,这是移植物功能正常者死亡的主要原因。本文综述了他克莫司移植后的毒性。他克莫司毒性是器官移植后受者发病率和死亡率的主要决定因素。因此,降低毒性已成为当务之急。为了减少副作用的发生,扩大移植物的生存,适当的初始和维持剂量他克莫司是必不可少的。影响他克莫司药代动力学的临床条件,如出血、全身性炎症和休克,都会导致他克莫司浓度的较大变化。此外,非结合血药浓度是监测不稳定患者接受最佳他克莫司剂量的重要合理参数。因此,监测他克莫司的方法是至关重要的,将有助于避免移植后早期他克莫司毒性。
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Tacrolimus toxicity in organ transplantation: an overview
Tacrolimus is a macrolide lactone antibiotic, and acts as a calcineurin inhibitor. It is widely used to prevent organ transplant rejection. It has been approved as first-line treatment after organ transplantation. Tacrolimus has narrow therapeutic range and wide individual variability in its pharmacokinetics. In organ transplantation, immunosuppression is associated with important risks, in particular, related to infections and cardiovascular diseases, which are the predominant causes of death in those with a functioning graft. This review focuses on toxicity of tacrolimus after transplantation. Tacrolimus toxicity is a major determinant of morbidity and mortality in organ recipients after transplantation. Therefore, reducing toxicities has become a priority. To decrease the incidence of side effects, and expand graft survival, the appropriate initial and maintenance dose of tacrolimus is essential. Clinical conditions that influence tacrolimus pharmacokinetics, such as hemorrhage, systemic inflammation and shock, all result in higher variations of tacrolimus concentrations. In addition, unbound plasma concentration is a major important reasonable parameter for monitoring of receiving optimal tacrolimus dosing in the unstable patient. Therefore, the approach of tacrolimus monitoring is vital and will support to avoid tacrolimus toxicity in the early days after transplantation.
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