RT Journal Article SR Electronic T1 HYDROXYLATION OF 14C-NIFLUMIC ACID BY PHENOBARBITAL-INDUCED RAT LIVER MICROSOMES JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 96 OP 103 VO 3 IS 2 A1 SHIH-JUNG LAN A1 THEODORE J. CHANDO A1 ERIC C. SCHREIBER YR 1975 UL http://dmd.aspetjournals.org/content/3/2/96.abstract AB 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%, whereas the 5-hydroxylase activity was increased 205%. Niflumic acid inhibited both the 4'- and 5-hydroxylases at concentrations greater than 1 mM. Competitive inhibition of 4'- or 5-hydroxylase was observed with SKF 525-A. WIN 13099 inhibited both hydroxylases noncompetitively. With freshly prepared microsomes, acetone, at concentrations up to 10% (v/v), enhanced 4'-hydroxylase markedly but had little effect on 5-hydroxylase. With 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. Copyright © 1975 by The American Society for Pharmacology and Experimental Therapeutics