Uptake, metabolism, and biliary secretion of 3'-methyl-N,N-dimethyl-4-aminoazobenzene (3'-Me-DAB) were studied in isolated rat liver which was perfused with protein-free fluorocarbon medium. [14C]3'-Me-DAB (5-10 nmol) was injected into the portal vein and allowed to recirculate. The recovery of radioactivity in bile was 7.5, 14, and 20% at 15, 30, and 45 min of injection, respectively. At 45 min, the liver contained an additional 17% of injected radioactivity. Azo dye metabolites in perfused liver differed from those in vivo; metabolites co-migrating with 3'-CHO-DAB and 3'-methyl-n,n-methyl) aminoazobenzene (Me-MAB) (and the parent compound 3'-Me-DAB) were present, while metabolites co-migrating with 3'-Me-4'-OH-AB and 3'-CH2OH-MAB were increased and metabolites co-migrating with 3'-CH2OH-DAB were decreased. In bile from perfused liver, metabolites co-migrating with 3'-CHO-DAB and 3'-Me-DAB were undetectable. When proteins from normal bile were injected into the portal vein 15 min after the administration of 3'-Me-DAB, the compounds co-migrating with 3'-Me-MAB, 3'-CHO-DAB, 3'-Me-4'-OH-AB, and 3'-CH2OH-MAB decreased, and compounds co-migrating with 3'-CH2OH-DAB increased in the liver; in bile, there was an increase in 3'-Me-MAB, 3'-CHO-DAB, and 3'-Me-4'-OH-MAB, while there was a decrease in N-Ac-3'-Me-4'-OH-AB and 3'-COOH-DAB. Appearance of protein-metabolite adducts in bile were also observed after addition of normal bile proteins to the perfusate. The results suggest that uptake and metabolism of 3'-Me-DAB and biliary secretion of many of its metabolites occur in the absence of circulating blood protein; some metabolites may require proteins in the circulation for their secretion into bile.
|Original language||English (US)|
|Number of pages||5|
|Journal||Drug Metabolism and Disposition|
|State||Published - 1987|
ASJC Scopus subject areas
- Pharmaceutical Science