METABOLISM OF INTRAVENOUS METHYLNALTREXONE IN MICE, RATS, DOGS AND HUMANS

were observed in rats. Dogs produced only one metabolite, MNTX-3-glucuronide (M9). In conclusion, MNTX was not extensively metabolized in humans. Conversion to methyl-6-naltrexol isomers (M4 and M5) and MNTX-3-sulfate (M2) were the primary pathways of metabolism in humans. MNTX was metabolized to a higher extent in mice than in rats, dogs, and humans. Glucuronidation was a major metabolic pathway in mice, rats and dogs, but not in humans. Overall, the data suggested species differences in the metabolism of MNTX