Sullivan H R, Roffey P, McMahon R E
Drug Metab Dispos. 1979 Mar-Apr;7(2):76-80.
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.
在大鼠中研究了一种新型抗炎药4'-乙炔基-2-氟联苯的吸收、代谢及血浆药代动力学。4'-[1-¹⁴C]乙炔基-2-氟联苯可从胃肠道定量吸收。放射性碳向尿液中的排泄量大于向胆汁中的排泄量。给药24小时后，大量放射性碳仍留在体内。血浆中唯一的代谢产物是(2-氟-4'-联苯基)乙酸，其也具有抗炎活性。给予较高剂量后，仍存在未变化的4'-乙炔基-2-氟联苯。给药后1小时内观察到(5-氟-4'-联苯基)乙酸的血浆浓度峰值。这种酸性代谢产物的表观血浆半衰期为4小时。主要的消除代谢产物是(4-羟基-2-氟-4'-联苯基)乙酸。体内和体外代谢研究表明，主要代谢途径涉及乙炔基部分C-H键的微粒体羟基化，重排后产生一种高活性的中间代谢产物2-氟-4'-联苯甲酮。
