Synthesis, kinetics and pharmacological comparison of a mutual prodrug of mefenamic acid to related physical mixture

Abstract

A gastrosparing NSAID devoid of ulcerogenic side effects has been designed, synthesized and evaluated. This novel mutual prodrug consists of mefenamic acid and salicylamide. The structure was confirmed by IR, 1H NMR, and mass spectroscopy. The kinetics of ester hydrolysis was studied at pH 2 and 7.4 and in human plasma by HPLC. The pharmacological activities (anti-inflammatory, analgesic and ulcerogenic) were evaluated and compared with data for the related physical mixture (mefenamic acid and salicylamide). Then, oxidative stress parameters (LPO, GSH, CAT and SOD) were also measured and the results were compared with those for the physical mixture. The obtained results indicate that the synthesized ester is chemically stable, biolabile, and possesses optimum lipophilicity. © 2014 Springer Science+Business Media.