Isolation of an immunosuppressive metabolite of FK506 generated by human microsome preparations

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / metabolism*
  • Anti-Bacterial Agents / pharmacology
  • Centrifugation
  • Chemical Fractionation
  • Chromatography, High Pressure Liquid
  • Cyclosporins / analysis*
  • Cyclosporins / metabolism
  • Humans
  • Immunosuppressive Agents / metabolism*
  • Immunosuppressive Agents / pharmacology
  • Lymphocyte Activation / drug effects
  • Microsomes, Liver / metabolism*
  • NADP
  • Rats
  • Rats, Inbred Strains
  • Spectrometry, Mass, Fast Atom Bombardment
  • Tacrolimus


  • Anti-Bacterial Agents
  • Cyclosporins
  • Immunosuppressive Agents
  • NADP
  • Tacrolimus