Metabolism of desloratadine by chimeric TK-NOG mice transplanted with human hepatocytes.

Metabolism of desloratadine by chimeric TK-NOG mice transplanted with human hepatocytes. Xenobiotica. 2019 Nov 05;:1-26 Authors: Uehara S, Yoneda N, Higuchi Y, Yoneda N, Yamazaki H, Suemizu H Abstract 1. Desloratadine is an antiallergic drug with species-dependent metabolic profiles in mice, rats, monkeys, and humans. We investigated whether humanized-liver mice could reproduce the reported human-specific in vivo metabolic profile for desloratadine in terms of the formation of 3-hydroxydesloratadine and its O-glucuronide.2. Hepatocytes prepared from humans and humanized-liver mice both preferentially catalyzed the formation of 3-hydroxydesloratadine and its O-glucuronide in vitro.3. After a single oral administration of desloratadine, plasma levels of desloratadine and its metabolites (3-hydroxydesloratadine and its O-glucuronide) in humanized-liver mice were lower and higher, respectively, than those in control mice.4. The amounts of 3-hydroxydesloratadine and its O-glucuronide excreted in humanized-liver mouse feces and urine were higher than those of the control mice, whereas 5- and 6-hydroxydesloratadine formation were predominant in the feces and urine samples from control mice. A significant correlation (r = 0.68) for the dose percentage of urinary and fecal metabolites of desloratadine was only observed between the humanized-liver mice and the reported values for humans.5. These results indicated that urinary 3-hydroxydesl...
Source: Xenobiotica - Category: Research Authors: Tags: Xenobiotica Source Type: research