Jusko W J
Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo 14260, USA.
Ther Drug Monit. 1995 Dec;17(6):596-601. doi: 10.1097/00007691-199512000-00009.
Tacrolimus (FK506) is a macrolide lactone which is used as an immunosuppressant agent for organ transplantation. Patient monitoring during clinical trials initially involved use of extraction/enzyme immunoassays (ELISA) for plasma and whole blood concentrations of FK506. Therapeutic concentrations of FK506 are approximately 0.4-1.2 ng/ml in plasma and 5-20 ng/ml in whole blood. Blood:plasma ratios are variable among patients and range from 11 to 114. A validation and quality assurance program was established to standardize procedures and assure concordance of ELISA analytic results from clinical sites participating in liver/kidney trials. HPLC/ELISA methods have been used for assessing assay specificity. Comparison of the ELISA method with a HPLC-MS procedure (TexMS) shows good correlation, but indicates metabolite inclusion in the ELISA. This method may be of value in conditions of altered FK-506 metabolism. Commercialization of the immunoassay has been made by Incstar with the ELISA and Abbott Laboratories with an IMx procedure; the two methods are generally comparable. Additional methods offering clinical promise are radioreceptor and pentamer complex ELISA assays. There are diverse methods offering sensitive quantitation but with varying specificity for tacrolimus in patient plasma and whole blood.
他克莫司（FK506）是一种大环内酯类内酯，用作器官移植的免疫抑制剂。临床试验期间的患者监测最初涉及使用萃取/酶免疫测定法（ELISA）来检测血浆和全血中FK506的浓度。FK506的治疗浓度在血浆中约为0.4 - 1.2 ng/ml，在全血中为5 - 20 ng/ml。患者之间的血：浆比值各不相同，范围为11至114。建立了一个验证和质量保证计划，以规范程序，并确保参与肝/肾试验的临床站点的ELISA分析结果的一致性。HPLC/ELISA方法已用于评估测定特异性。ELISA方法与HPLC-MS程序（TexMS）的比较显示出良好的相关性，但表明ELISA中包含代谢物。该方法在FK-506代谢改变的情况下可能具有价值。免疫测定的商业化已由Incstar通过ELISA方法以及雅培实验室通过IMx程序实现；这两种方法通常具有可比性。具有临床前景的其他方法是放射受体和五聚体复合物ELISA测定法。有多种方法可提供灵敏的定量，但对患者血浆和全血中的他克莫司具有不同的特异性。
