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Inhibition of ileal bile acid transport by cyclosporin A in rat
Author(s) -
SAUER P.,
KLÖTERSPLACHKY P.,
STIEHL A.
Publication year - 1995
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.1995.tb01985.x
Subject(s) - ileum , bile acid , medicine , taurocholic acid , glycocholic acid , absorption (acoustics) , cholestasis , endocrinology , chemistry , perfusion , in vivo , enterohepatic circulation , cholic acid , biology , physics , microbiology and biotechnology , acoustics
. Chronic administration of cyclosporin A may induce cholestasis and this effect has been attributed to impaired hepatic bile salt synthesis, metabolism and transport. We investigated the effect of cyclosporin A on intestinal absorption of bile acids in the ileum of rat. Ileal bile acid absorption was measured by in vivo intestinal perfusion with cyclosporin A and the solvent Cremophor EL. During ileal perfusion with 25 μM glycocholic acid, the concentration of 2.8 mm cyclosporin A inhibited intestinal bile acid absorption on average by 34%. Additional experiments were performed with everted gut sacs of the distal ileum to evaluate active absorption. A dose and time dependent inhibition of the active intestinal absorption of bile acids was found, with a 50% transport inhibition at an average cyclosporin A concentration of 2.69mmolL ‐' . Thus, cyclosporin A inhibits the active intestinal absorption of bile acids which may influence bile acid synthesis, turnover and secretion and may contribute to cyclosporin A induced cholestasis.