Hydroxylation of 14-C-niflumic acid by phenobarbital-induced rat liver microsomes.
Hydroxylation of niflumic acid to 4'-hydroxyniflumic acid and 5-hydroxyniflumic acid by rat liver microsomes from untreated animals or phenobarbital-pretreated animals has been demonstrated. Pretreatment of rats with phenobarbital (50 mg/kg) increased the 4'-hydroxylase activity 53%, whreas the 5-hydroxylase activity was increased 205%. Niflumic acid inhibited of 4'- or 5-hydroxylase was observed with SKF 525-A. WIN 13099 inhibited both hydroxylases noncompetitvely. With freshly prepared microsomes, acetone, at concentrations frozen and aged microsomes, maximum enhancement of 4'-hydroxylase was obtained at 5% acetone; little or no effect on 5-hydroxylase was observed at the same concentration. At 10% acetone, the 4'- and 5-hydroxylases were inhibited 33 and 73% respectively. The data indicate that at least two different enzyme systems are involved in the hydroxylation of niflumic acid by the microsomes of rat liver.
D000818:Animals; D002250:Carbon Radioisotopes; D004790:Enzyme Induction / Q000187:drug effects; D007700:Kinetics; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009539:Nicotinic Acids / Q000378:metabolism*; D009544:Niflumic Acid / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats
D002250:Carbon Radioisotopes; D009539:Nicotinic Acids; D009544:Niflumic Acid; D006899:Mixed Function Oxygenases; D010634:Phenobarbital