FK506 (tacrolimus), a novel immunosuppressant in organ transplantation: clinical, biomedical, and analytical aspects.
FK506 (tacrolimus), a novel immunosuppressant in organ transplantation: clinical, biomedical, and analytical aspects.
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DOI：
10.1093/clinchem/39.11.2219
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发表时间：
1993-11
影响因子：
9.3
通讯作者：
P. Wallemacq;R. Reding
中科院分区：
文献类型：
--
作者：
P. Wallemacq;R. Reding
大环内酯类免疫抑制剂FK 506（他克莫司）是一种强大的和选择性的抗T淋巴细胞剂，发现于1984年。该药剂分离自真菌Streptomyces tsukubaensis，其作用机制类似于环孢菌素。实验数据于1987年首次发表，两年后在匹兹堡开始了临床试验。该药物具有强大的肝营养作用，这可以解释其在肝移植中的成功。在肝移植受者中获得了特别令人鼓舞的结果，这表明与其他免疫抑制剂相比，其风险/获益比更低。然而，最近的数据显示，该药物并非没有毒性（主要是肾毒性），这应该是需要仔细监测血液的百分比。已经描述了几种分析方法，有些令人满意，其他的不适合常规监测。仍然缺乏用于临床药代动力学目的的常规测定生物液体中母体药物浓度的特定方法。尽管在治疗药物监测方面有更多的经验，但FK 506浓度与疗效或毒性之间的相关性仍不清楚。需要更多的研究来更好地理解和确定FK 506在器官移植和治疗自身免疫性疾病中的适当使用。
The macrolide immunosuppressant FK506 (tacrolimus) is a powerful and selective anti-T-lymphocyte agent that was discovered in 1984. This agent, isolated from the fungus Streptomyces tsukubaensis, has a mechanism of action similar to that of cyclosporine. Experimental data were first published in 1987, and clinical trials were started 2 years later in Pittsburgh. The drug has a potent hepatotrophic effect, which could explain its success in liver transplantation. Particularly encouraging results were obtained in liver allograft recipients, suggesting a lower risk/benefit ratio than with other immunosuppressants. However, recent data show that the drug is not devoid of toxicity (mainly nephrotoxicity), which should the percent the need for careful blood monitoring. Several methods of analysis have been described, some satisfactory, others inadequate for routine monitoring. There is still a lack of specific methods to determine routinely the parent drug concentrations in biological fluids for clinical pharmacokinetics purposes. Despite greater experience in therapeutic drug monitoring, the correlation between FK506 concentrations and efficacy or toxicity is still unclear. More investigations are required to better understand and determine the appropriate use of FK506 in organ transplantation and treating autoimmune diseases.