In vitro glucuronidation of D-23129, a new anticonvulsant, by human liver microsomes and liver slices

1. The metabolic profile of D-23129, a new anticonvulsant agent, was studied in vitro using human liver microsomes and fresh liver slices. 2. Oxidative metabolism appeared to be minimal with D-23129. The percent mean total radioactivity not associated with the parent compound recovered from oxidative metabolism studies from three individual liver donors was 0 7% 0 6 SD and was not significantly different from \ [C]-D-23129 incubated with heat inactivated microsomes, mean 0 5% 0 4 SD. 3. Phase II conjugation dominated the metabolism of D-23129 producing two distinct N -glucuronides as the primary metabolites. These metabolites were identified by electrospray ionization LC MS. 4. The apparent K for one of the glucuronide metabolites was determined in human m liver microsome preparations from two individual liver donors to be 131 and 264 mu M respectively. V determined for the same microsomal preparations yielded 48 9 and max 59 9 pmol min mg protein.