The Metabolism of 5-(4-Acetamidophenyl)Pyrazin-2(1H)-One in Rat, Dog and Cynomolgus Monkey

Abstract

1. The metabolism and disposition of ¹⁴C-acetamidophenyl pyrazinone has been studied in rat, dog and cynomolgus monkey. The compound was well absorbed and rapidly excreted in urine and faeces by all three species.

2. Distribution of ¹⁴C-pyrazinone was rapid and extensive with the exception of the central nervous system where concentrations were at, or below, the limit of detection.

3. Whereas, in in vitro studies, metabolites (but not the parent compound) weakly inhibited some activities of the cytochrome P-450 system, there was evidence from in vivo studies in the rat that the compound and/or its metabolite(s) are weak selective inducers of cytochrome P-450.

4. Metabolite patterns were similar in all three species. The major route of metabolism was glucuronidation at the oxygen of the pyrazinone ring. Other metabolites originated from metabolism by gut microflora with subsequent hepatic metabolism.