Use of the NIH shift to determine the relative contribution of competing pathways of aniline metabolism in the rat.
The retention of tritium in urinary p-aminophenol and p-hydroxyacetanilide was determined following the administration of p-3H-aniline or p-3H-acetanilide to rats. When p-3H-aniline (1.5 mmol/kg, ip) was given to rats, the retention of tritium in urinary p-aminophenol and p-hydroxyacetanilide was 15% and 38%, respectively. Similar results were obtained following the administration of p-3H-acetanilide (1.5 mmol/kg). However, when p-3H-acetanilide was given to rats which had been pretreated with bis-(p-nitrophenyl)phosphate to block the deacetylation capacity, urinary 3H-p-hydroxyacetanilide was recovered with 53% retention of tritium. The data indicate that, at the doses studied: the primary route of aniline metabolism is via sequential acetylation and hydroxylation, and deacetylation plays a significant role in the disposition of acetanilide.
D000107:Acetylation; D000814:Aniline Compounds / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D006900:Hydroxylation; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009596:Nitrophenols / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000814:Aniline Compounds; D009596:Nitrophenols; C002887:bis(4-nitrophenyl)phosphate; C023650:aniline