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Cyclosporin metabolism by human gastrointestinal mucosal microsomes.
Author(s) -
Webber IR,
Peters WH,
Back DJ
Publication year - 1992
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1992.tb04098.x
Subject(s) - microsome , metabolism , medicine , pharmacology , chemistry , gastroenterology , biochemistry , in vitro
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.