TY - JOUR T1 - Stereoselective glucuronidation of zileuton isomers by human hepatic microsomes. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 149 LP - 153 VL - 23 IS - 1 AU - D J Sweeny AU - H N Nellans Y1 - 1995/01/01 UR - http://dmd.aspetjournals.org/content/23/1/149.abstract N2 - The glucuronidation of the R-isomer and S-isomer of the 5-lipoxygenase inhibitor zileuton was examined using human hepatic microsomes. The glucuronidation of both isomers followed Michaelis-Menten kinetics, but glucuronidation rates were between 3.6- and 4.3-fold greater for the S-isomer. The apparent Km's (microM) for the R-isomer (392.9 +/- 35.9) and S-isomer (322.5 +/- 22.0) glucuronidation were similar, whereas the apparent Vmax (nmol/mg protein/min) was 3.4-fold greater for the S-isomer (5.2 +/- 0.7). In combination, each isomer competitively inhibited the glucuronidation of its antipode. The average Ki (microM) determined for S-isomer inhibition of R-isomer glucuronidation (197.8 +/- 61.3) was 2.4-fold lower than the Ki for the reciprocal interaction. These data indicate that the glucuronidation of the zileuton isomers in human hepatic microsomes is stereoselective. This stereoselective glucuronidation may be the basis for the more rapid clearance of the S-isomer observed in humans receiving zileuton. ER -