Enterohepatic circulation of indomethacin and its role in intestinal irritation.
作者： Daniel E. Duggan , Kaye F. Hooke , Ronald M. Noll , K. Chiu Kwan
DOI: 10.1016/0006-2952(75)90450-5
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摘要: Abstract The accumulative biliary secretion of indomethacin and its conjugate(s), based upon clearance constants areas portal peripheral plasma profiles, has been determined for five laboratory species estimated man. This parameter, termed Σ bile % , ranges approximately 30-fold from 13 per cent dosage in the rabbit to 362 dog, provides a quantitative correlate wide variation sensitivity indomethacin-related intestinal lesions. Extrapolation vs. toxicity relationship man predicts therapeutic ratio ca. 20:1 with respect irritation. pharmacokinetic modeling derived present purpose should be general utility quantitation enterohepatic recycling drugs or metabolites whose loci intended untoward effects include liver gut.
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