Species-dependent enantioselective glucuronidation of carprofen
作者： R. MAIRE-GAUTHIER , T. BURONFOSSE , J. MAGDALOU , R. HERBER , S. BESSE
关键词: Microsome 、 Substrate (chemistry) 、 Stereochemistry 、 Microsoma 、 Carprofen 、 Metabolism 、 Pharmacology 、 Chemistry 、 Glucuronidation 、 Stereoselectivity 、 Pharmacokinetics
摘要: 1. The stereoselective glucuronidation of carprofen, a non-steroidal anti-inflammatory drug, was investigated in vitro using microsomes prepared from liver different species (rat, dog, horse, sheep and man) or UGT2B1 expressed fibroblasts. 2. Km towards the drug very similar among these for two menantiomers, whereas Vmax varied substantially according to animal used. rat exhibited high other species, including man, presented low stereoselectivity. R-enantiomer glucuronidated at more efficient rate than its enantiomorph, better substrate (in terms Vmax/Km). 3. To explain enantioselective disposition carprofen man species,the ratio enzymatic efficacies (Vmax/Km) were compared with max m pharmacokinetic parameters AUCs. basic hypothesis that intrinsic clearance reflect behaviour seemed substantiated when w...
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