biphenylylacetic-acid and Edema

A novel mutual prodrug consisting of 4-biphenylacetic acid (BPA) and quercetin tetramethyl ether (QTME) has been synthesized as a gastrosparing NSAID, devoid of ulcerogenic side effects. The physicochemical properties, including aqueous solubility, partition coefficient, chemical stability and enzymatic hydrolysis of synthesized derivative have been studied to assess its prodrug potential. Its antiinflammatory, antiulcer and analgesic activities were also evaluated. The results indicated that BPA-QTME derivative is chemically stable, biolabile and possesses optimum lipophilicity. The synthesized compound also exhibited retention of antiinflammatory activity with reduced ulcerogenicity. Based on these observations, the therapeutic potential of this mutual prodrug is discussed.

Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Drug Design; Drug Stability; Drug-Related Side Effects and Adverse Reactions; Edema; Enzymes; Gastrointestinal Tract; Humans; Hydrolysis; Male; Mice; Phenylacetates; Prodrugs; Quercetin; Rats; Solubility; Ulcer

4-Biphenylacetic acid, a potent non-steroidal anti-inflammatory agent forms a solid inclusion complex with beta-cyclodextrin in a 1:1 molar ratio, which exhibits better solubility and dissolution characteristics than the uncomplexed drug. Following oral administration of the complex to rats, quicker and higher drug plasma concentrations can be achieved than with the drug alone. Parallel studies, using the carrageenan paw oedema test, demonstrate a greater anti-inflammatory activity of the complex (ED50 of 2.9 mg kg-1 for the complex and of 6.2 mg kg-1 for the free drug). The complex displayed a better gastric tolerability in the rat than drug alone.

Topics: Administration, Oral; Animals; beta-Cyclodextrins; Biological Availability; Carrageenan; Cyclodextrins; Edema; Male; Phenylacetates; Rats; Rats, Inbred Strains; Stomach Ulcer