title: Cyclosporin metabolism by human gastrointestinal mucosal microsomes.
abstract: 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.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Liverpool.
authors.forename: I R
authors.initials: IR
authors.lastname: Webber
authors.forename: W H
authors.initials: WH
authors.lastname: Peters
authors.forename: D J
authors.initials: DJ
authors.lastname: Back
mesh_terms: D001682:Biological Availability; D015153:Blotting, Western; D016572:Cyclosporine / Q000378:metabolism* / Q000493:pharmacokinetics; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008861:Microsomes / Q000201:enzymology / Q000378:metabolism*; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism
chemical_list: D007527:Isoenzymes; D016572:Cyclosporine; D003577:Cytochrome P-450 Enzyme System