Metabolism of a dopamine receptor partial agonist in rats, including an unusual N-dearylation reaction.

The metabolism of 3,4-dihydro-7-[4-(1-naphthalenyl)-1-piperazinyl]butoxy]-1,8-naphthyridin-2(1H)-one (NPBN) was investigated in rats. Animals were administered 30 mg/kg NPBN that was labeled with both tritium and carbon-14. The mass recovery of drug-related material was 96-98%, with almost all material excreted in feces.

Assessment of a micropatterned hepatocyte coculture system to generate major human excretory and circulating drug metabolites.

Metabolism is one of the important determinants of the overall disposition of drugs, and the profile of metabolites can have an impact on efficacy and safety. Predicting which drug metabolites will be quantitatively predominant in humans has become increasingly important in the research and development of new drugs. In this study, a novel micropatterned hepatocyte coculture system was evaluated for its ability to generate human in vivo metabolites.