Wallemacq P E, Reding R
Department of Clinical Biochemistry, University Hospital St. Luc, University of Louvain, Brussels, Belgium.
Clin Chem. 1993 Nov;39(11 Pt 1):2219-28.
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.
大环内酯类免疫抑制剂FK506（他克莫司）是一种强效且具有选择性的抗T淋巴细胞药物，于1984年被发现。这种从筑波链霉菌中分离出来的药物，其作用机制与环孢素相似。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，表明其风险/效益比低于其他免疫抑制剂。然而，最近的数据表明该药物并非没有毒性（主要是肾毒性），这就需要进行仔细的血液监测。已经描述了几种分析方法，有些令人满意，有些则不足以用于常规监测。目前仍然缺乏用于临床药代动力学目的、常规测定生物体液中母体药物浓度的特异性方法。尽管在治疗药物监测方面有了更多经验，但FK506浓度与疗效或毒性之间的相关性仍不清楚。需要进行更多研究，以更好地理解并确定FK506在器官移植和自身免疫性疾病治疗中的适当用法。
