Metabolism and Excretion of RWJ-333369 [1,2-Ethanediol, 1-(2-Chlorophenyl)-, 2-carbamate, (S)-] in Mice, Rats, Rabbits, and Dogs

• DOI: 10.1124/dmd.106.012336
• Publication Date: 2007-01-13T01:34:47Z
• Authors: Rao N.V.S. Mamidi; Geert Mannens; Pieter Annaert; Jan Hendrickx; Ivo Goris; Mark Bockx; Cor G.M. Janssen; Mark Kao; Michael F. Kelley; Willem Meuldermans
• Keywords: Carbamate

The in vivo metabolism and excretion of RWJ-333369 [1,2-ethanediol, 1-(2-chlorophenyl)-, 2-carbamate, (<i>S</i>)-], a novel neuromodulator, were investigated mice, rats, rabbits, dogs after oral administration ¹⁴C-RWJ-333369. Plasma, urine, feces samples collected, assayed for radioactivity, profiled metabolites. In almost all species, the administered radioactive dose was predominantly excreted urine (&gt;85%) with less than 10% feces. Excretion radioactivity rapid nearly complete at 96 h dosing species. Unchanged drug minimal (&lt;2.3% dose) primary metabolic pathways <i>O</i>-glucuronidation (rabbit &gt; mouse dog rat) hydrolysis carbamate ester followed by oxidation to 2-chloromandelic acid. latter metabolite subsequently metabolized parallel 2-chlorophenylglycine 2-chlorobenzoic acid (combined hydrolytic oxidative pathways: rat rabbit). Other present species included chiral inversion combination sulfate conjugation (directly and/or following hydroxylation RWJ-333369). Species-specific pathways, including <i>N</i>-acetylation (mice, dogs) arene glutathione (mice rats), more predominant rodents other Consistent human metabolism, multiple renal mainly involved elimination its metabolites animal major plasma circulating drug-related substance preclinical humans.