Isolation of an immunosuppressive metabolite of FK506 generated by human microsome preparations
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U Christians1, H H Radeke, R Kownatzki
1Institut für Allgemeine Pharmakologie, Medizinische Hochschule Hannover, Germany.
Clinical Biochemistry
|June 1, 1991
Abstract:
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.