STEREOSELECTIVE DISPOSITION OF NAPROXEN GLUCURONIDE IN THE RAT

The disposition of R- and S-naproxen glucuronides were investi-gated after intravenous administration (-1.5 mg/kg) to normal male Sprague-Dawley rats and to rats pretreated with phenyl-methylsulfonylfluoride, an inhibitor of esterases. The relative sta-bility of the two glucuronides also was measured in vitro. Both diastereomers were hydrolyzed rapidly in vivo, liberating naproxen, but R-naproxen glucuronide was hydrolyzed faster than the corre-sponding S-diastereomer. This difference resufted in a larger plasma AUCN.P.AUCN.P0 ratio for the R-glucuronide. There was, however, no marked difference in the apparent clearance of the R-and S-diastereomers. Administration of phenylmethylsulfonylfluo-ride had no significant effect on the disposition of the two diaste-reomers. In 0.15 M phosphate buffer (pH 7.4) at 37#{176}C,the fastest degradation process for both diastereomers in vitro was acyl mi-gration. Our resufts show that R-naproxen glucuronide is mor