Gender-related differences in metabolism of the enantiomers of trans tramadol and trans O-demethyltramadol in rat liver microsomes / 药学学报

ABSTRACT

<p><b>AIM</b>To investigate the gender-related differences in the metabolism of trans tramadol (trans T) enantiomers and the glucuronidation of trans O-demethyltramadol (M1) enantiomers.</p><p><b>METHODS</b>In vitro, trans T or M1 were separately incubated with liver microsomes of male or female rats. The concentrations of the enantiomers of trans T and M1 were determined by an HPCE method.</p><p><b>RESULTS</b>Compared with (+)-enantiomers, (-)-trans T was preferentially metabolized, and (-)-M1 was produced faster in rat liver microsomes. (+)-M1 and (-)-M1 were preferentially glucuronidated in the liver microsomes of male and female rats, respectively. Compared with those in male rat liver microsomes, the enantiomeric ratios of CLint for M1 formation and M1 glucuronidation were more deviated from 1 in female rat liver microsomes.</p><p><b>CONCLUSION</b>In vitro, trans T metabolism, M1 formation and M1 glucuronidation were found to be stereoselective in rat liver microsomes. There were gender-related differences in the stereoselectivity in M1 formation and M1 glucuronidation, with a larger extent in female rat liver microsomes.</p>