TY - JOUR T1 - In vitro and in vivo biotransformations of the potent leukotriene D4 antagonist verlukast in the rat. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 383 LP - 389 VL - 20 IS - 3 AU - D Nicoll-Griffith AU - J Yergey AU - L Trimble AU - H Williams AU - R Rasori AU - R Zamboni Y1 - 1992/05/01 UR - http://dmd.aspetjournals.org/content/20/3/383.abstract N2 - Verlukast, (S)3-((((3-(2-(7-chloroquinolin-2-yl)-(E)-ethenyl)phenyl)- 3-dimethylamino-3-oxopropylthio)methyl)thio)propionic acid, formerly known as MK-679, is a potent leukotriene D4 antagonist. Verlukast was incubated with rat liver microsomes under oxidative conditions to generate five metabolites, which were identified as the four possible isomeric monosulfoxides (M1-M4), and the N-hydroxymethyl amide (M5). This latter metabolite loses the elements of formaldehyde to yield the N-monomethyl amide (M6). These metabolites were isolated from a large microsomal incubation and were characterized by UV, 1H-NMR, and fast atom bombardment-MS. These data were identical to those obtained from synthetically prepared standards. Microsomal incubations of verlukast supplemented with UDP-glucuronic acid yielded the acyl glucuronide metabolite (M7), which was isolated and characterized by UV, 1H-NMR, and fast atom bombardment-M5. Verlukast was regenerated from M7 upon treatment with either beta-glucuronidase or strong aqueous base (pH greater than 11). The metabolites described above were all detected in bile collected from a rat dosed with verlukast. ER -