The pharmacology of fenbufen, 3-(4-biphenylylcarbonyl)propionic acid, and 4-biphenylacetic acid, interesting antiinflammatory-analgesic agents

Abstract

Fenbufen [3-(4-biphenylylcarbonyl)propionic acid] was shown to be an orally and parenterally effective nonsteroidal antiinflammatory analgetic and antipyretic agent in animals. Like clinically useful drugs (aspirin, phenylbutazine and indomethacin) it has potent antiinflammatory activity in a wide spectrum of laboratory tests in mice, rats, guinea pigs, and dogs and was of particular interest since it appears to have high analgetic efficacy and a long duration of antiinflammatory and analgetic action. While shown to have ulcerogenic potential in rats at toxic doses, it appeared to have a superior margin of gastrointestinal safety in treatment of dogs with urate synovitis. Evidence was also presented to show that BPAA (4-biphenylacetic acid), a metabolite of fenbufen, has a similar profile of antiinflammatory activity, although appearing to produce slightly more gastrointestinal injury. It appears that BPAA may be the agent responsible for at least part of fenbufen's pharmacologic effects. The data presented suggest that fenbufen has the potential to be used safely and effectively to provide relief for patients with inflammatory disease.

Fenbufen in Osteoarthritis of the Hip

“…In comparison with equal doses o f other nonste roidal drugs (e.g. indometacin, phenylbuta zone and acetylsalicylic acid) fenbufen was found to be considerably more effective in increasing the reaction threshold to pain [6].…”

Effects on Gastric Prostaglandin Synthesis Produced by Fenbufen, a New Nonsteroidal Anti-Inflammatory Agent with Low Gastrointestinal Toxicity

“…From both preclinical and clinical investigations an important finding has emerged in that, relative to other NSAIs. fen bufen treatment is associated with a remark ably low incidence of serious gastrointestinal adverse effects such as gastric ulcers, perfora tion and significant gastrointestinal bleeding [22,31]. The basis for these observations is examined in detail in this communication.…”

“…(1) Biphenylacetic acid was more potent than fenbufen in most anti-inflammatory, analgesic, and antipyretic assays [31,32], Moreover, biphenylacetic acid, but not fen bufen. showed anti-inflammatory activity when applied locally to UV-irradiated skin or instilled in urate-challenged joints [31]; and topical application of biphenylacetic acid, but not fenbufen, suppressed arachidonic acid-induced increases in the intraocular pressure of rabbit eyes [35].…”

“…showed anti-inflammatory activity when applied locally to UV-irradiated skin or instilled in urate-challenged joints [31]; and topical application of biphenylacetic acid, but not fenbufen, suppressed arachidonic acid-induced increases in the intraocular pressure of rabbit eyes [35].…”

Pharmacological Properties of Fenbufen

“…In this paper, the pharmacologic proper ties of fenbufen and 4-biphenylacetic acid in the various models of inflammation and analgesia are reviewed [10,11].…”