Evaluation of the marmoset as a model species for drug glucuronidation

Abstract

1. The in vitro glucuronidation of a wide range of compounds has been studied in microsomes prepared from marmoset liver and kidney. These studies have been undertaken to evaluate the marmoset as a model species for drug glucuronidation and for comparison with conjugation by other species. 2. The compounds studied were glucuronidated by marmoset liver microsomes to varying extents (e.g. naproxen CL int 0.4 µl min -1 mg -1, 1-naphthol CLint 43 µl min -1 mg -1). Both marmoset and rat liver microsomes glucuronidated morphine at the 3-position (marmoset CL int 19 µl min -1 mg -1, rat CL int 6.3 µl min -1 mg -1) but glucuronidation at the 6-position was below the level of radiodetection in both species. 3. Interestingly, marmoset liver microsomes were able to catalyse the glucuronidation of the tertiary amine imipramine to a significant extent (0.05 nmol min -1 mg -1). However, no glucuronidation was detected by rat liver microsomes. 4. Conjugation of a range of substrates was detectable by marmoset kidney microsomes in contrast to rat kidney microsomes, which only catalysed the glucurondation of bilirubin and 1-naphthol (CLint 17 µl min -1 mg -1 and 18 µl min -1 mg -1, respectively). 5. This report and previous work in dog and human tissue microsomes suggest that the marmoset may be an alternative animal model for human drug glucuronidation, especially when the pathway of drug glucuronidation is known to differ between lower laboratory species and man.