Christians U, Radeke H H, Kownatzki R, Schiebel H M, Schottmann R, Sewing K F
Institut für Allgemeine Pharmakologie, Medizinische Hochschule Hannover, Germany.
Clin Biochem. 1991 Jun;24(3):271-5. doi: 10.1016/0009-9120(91)80019-y.
Metabolism of FK506, a 23 member macrolide under clinical investigation as immunosuppressant after transplantation, was studied using human liver microsomes. Two fractions isolated by semi-preparative HPLC were identified by negative fast atom bombardment mass spectrometry as FK506 metabolites with mass peaks at m/z = 790 indicating demethylation of the mother compound. The immunosuppressive activity of one metabolite was evaluated in a ConA-stimulated peripheral rat lymphocyte assay. FK506 had an IC50 of 0.186 nmol/L and the metabolite tested of 1.89 nmol/L.
FK506是一种含23个成员的大环内酯类化合物，目前正作为移植后免疫抑制剂进行临床研究。利用人肝微粒体对其代谢情况进行了研究。通过半制备高效液相色谱法分离得到的两个组分，经负快原子轰击质谱鉴定为FK506代谢产物，其质荷比（m/z）为790的质谱峰表明母化合物发生了去甲基化。在刀豆蛋白A刺激的大鼠外周淋巴细胞试验中评估了其中一种代谢产物的免疫抑制活性。FK506的半数抑制浓度（IC50）为0.186纳摩尔/升，所测试的代谢产物的IC50为1.89纳摩尔/升。
