Studies on the in vitro inversion of flurbiprofen

This paper reports in vitro studies on the metabolic inversion of flurbiprofen (FL), an arylpropionic acid antiinflammatory agent (2-APA). The inversion was studied with both rac-FL and R-FL, by incubation with rat hepatic microsomes, in the presence of either CoASH and ATP or NADPH. The two isomers of the drug were separated as their (+)-(R)-1-phenylethylamides by direct phase high-performance liquid chromatography on a silica gel column with an achiral mobile phase. The inversion was more pronounced in the presence of CoASH and ATP for both the racemate and the R-isomer, which supports the key role of CoA thioesters in the metabolic inversion of profens. The inversion observed in the presence of NADPH suggests that, when the incubation is run with hepatic microsomes, a CYP450-mediated pathway is also active. In order to get more insight into the CYP450-mediated inversion pathway, we studied the effect of irradiating microsomes with a low dose of He-Ne laser radiation (0.2 J). Such irradiation caused a significant increase in inversion at all times studied and normalized the anomalous value of inversion observed at 15 min in his pathway. Chirality 9:317–319, 1997. © 1997 Wiley-Liss, Inc.