Isolation of an immunosuppressive metabolite of FK506 generated by human microsome preparations.
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.
Christians
U
U
Institut für Allgemeine Pharmakologie, Medizinische Hochschule Hannover, Germany.
Radeke
H H
HH
Kownatzki
R
R
Schiebel
H M
HM
Schottmann
R
R
Sewing
K F
KF
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D002498:Centrifugation; D005591:Chemical Fractionation; D002851:Chromatography, High Pressure Liquid; D003524:Cyclosporins / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008862:Microsomes, Liver / Q000378:metabolism*; D009249:NADP; D051381:Rats; D011919:Rats, Inbred Strains; D016339:Spectrometry, Mass, Fast Atom Bombardment; D016559:Tacrolimus
D000900:Anti-Bacterial Agents; D003524:Cyclosporins; D007166:Immunosuppressive Agents; D009249:NADP; D016559:Tacrolimus