PT  - JOURNAL ARTICLE
AU  - H R Sullivan
AU  - P Roffey
AU  - R E McMahon
TI  - Biotransformation of 4'-ethynl-2-fluorobiphenyl in the rat. In vitro and in vivo studies.
DP  - 1979 Mar 01
TA  - Drug Metabolism and Disposition
PG  - 76--80
VI  - 7
IP  - 2
4099  - http://dmd.aspetjournals.org/content/7/2/76.short
4100  - http://dmd.aspetjournals.org/content/7/2/76.full
SO  - Drug Metab Dispos1979 Mar 01; 7
AB  - The absorption, metabolism, and plasma pharmacokinetics of a novel anti-inflammatory agent, 4'-ethynyl-2-fluorobiphenyl, was studied in the rat. 4'-[1-14C]Ethynyl-2-fluorobiphenyl was quantitatively absorbed from the gastrointestinal tract. Excretion of radiocarbon into urine was greater than excretion into bile. Appreciate amounts of radiocarbon remained in the carcass 24 hr after dosing. The only metabolite in plasma was (2-fluoro-4'-biphenylyl)acetic acid, which also possessed anti-inflammatory activity. Unchanged 4'-ethynyl-2-fluorobiphenyl was present after administration of higher doses. Peak plasma concentrations of (5-fluoro-4'-biphenylyl)acetic acid were observed within 1 hr of administration. The apparent plasma half-life of this acidic metabolite was 4 hr. The major eliminated metabolite was (4-hydroxy-2-fluoro-4'-biphenylyl)acetic acid. In vivo and in vitro metabolism studies suggest that the major metabolic pathway involves microsomal hydroxylation of the C-H bond of the ethynyl moiety to yield, after rearrangement, a highly reactive intermediate metabolite, 2-fluoro-4'-biphenylylketene.