Cyclosporin metabolism by human gastrointestinal mucosal microsomes

Br J Clin Pharmacol. 1992 Jun;33(6):661-4. doi: 10.1111/j.1365-2125.1992.tb04098.x.


The in vitro metabolism of the immunosuppressant cyclosporin (CsA) by human gastrointestinal mucosal microsomes has been studied. Macroscopically normal intestinal (n = 4) and liver (n = 2) tissue was obtained from kidney transplant donors, and microsomes prepared. Intestinal metabolism was most extensive with duodenal protein (15% conversion to metabolites M1/M17 after 2 h incubation at 37 degrees C; metabolite measurement by h.p.l.c). Western blotting confirmed the presence of P-4503A (enzyme subfamily responsible for CsA metabolism) in duodenum and ileum tissue, but not in colon tissue. The results of this study indicate that the gut wall may play a role in the first-pass metabolism of CsA, and could therefore be a contributory factor to the highly variable oral bioavailability of CsA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Availability
  • Blotting, Western
  • Cyclosporine / metabolism*
  • Cyclosporine / pharmacokinetics
  • Cytochrome P-450 Enzyme System / metabolism
  • Humans
  • Intestinal Mucosa / metabolism*
  • Isoenzymes / metabolism
  • Microsomes / enzymology
  • Microsomes / metabolism*
  • Microsomes, Liver / enzymology
  • Microsomes, Liver / metabolism


  • Isoenzymes
  • Cyclosporine
  • Cytochrome P-450 Enzyme System