Drug metabolism in rats with arthritis induced by 6-sulfanilamidoindazole (6-SAI).
Hexobarbital sleeping time was prolonged and ethylmorphine N-demethylation was inhibited after a single dosage or seven administration of 6-SAI to old rats. These effects were independent of the development of arthritis. Changes in cytochrome P-450 concentration after 6-SAI treatment were insignificant and thus not responsible for the decrease in drug metabolism. In vitro 6-SAI inhibited ethylmorphine N-demethylation; the inhibition was of a mixed type. 6-SAI bound to cytochrome P-450 and induced a type II spectrum. The magnitude of hexobarbital-induced type I spectral changes was diminished by 6-SAI. It is concluded that 6-SAI inhibits cytochrome P-450-dependent drug metabolism by binding to cytochrome P-450.
D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000378:metabolism*; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006591:Hexobarbital / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012890:Sleep / Q000187:drug effects; D013424:Sulfanilamides / Q000494:pharmacology*
D007191:Indazoles; D004364:Pharmaceutical Preparations; D013424:Sulfanilamides; C009347:6-sulfanilamidoindazole; D003577:Cytochrome P-450 Enzyme System; D006591:Hexobarbital; D006899:Mixed Function Oxygenases