Characterization of the in vitro glucuronidation of flurbiprofen enantiomers.

摘要: To investigate the glucuronidation of R- and S-enantiomers nonsteroidal antiinflammatory drug, flurbiprofen, by liver microsomes several mammals, including humans, a new reliable HPLC method for separation quantification corresponding diastereoisomeric glucuronides has been developed. Interspecies comparison revealed that flurbiprofen was highly efficient with monkeys, rats, guinea pigs (in decreasing ranking order). Gunn which present genetic defect in bilirubin UDP-glucuronosyltransferase (UGT) isoforms, were still able to glucuronidate drug. The R-enantiomer glucuronidated faster than S-form rats humans. Although KM rat UGT same order magnitude (apparent 0.52 0.57 mM, respectively), apparent Vmax's significantly different (9.34 5.48 nmol/min.mg protein). Regardless enantiomer considered, strongly increased up 5-fold treatment phenobarbital and, at lower extent, 3-methylcholanthrene. In contrast, ciprofibrate markedly decreased activity. Glucuronidation R-flurbiprofen more enhanced S-antipode. Each could weakly inhibit its antipode noncompetitive way. Ki 0.51 mM as substrate, 0.37 S-enantiomer. On other hand, UGT2B1 isoform, stably expressed V79 cells, an appreciable amount.(ABSTRACT TRUNCATED AT 250 WORDS)