Mefenamic acid prodrugs and codrugs - two decades of development

Abstract

Prodrugs are bioreversible derivatives of drug molecules that undergo intermolecular or intramolecular reactions by enzymatic or chemical biotransformation in the human body to give the corresponding active parent drugs and a non-toxic promoiety. Prodrugs have been extensively and successfully used as a chemical tool for modification of the physicochemical, pharmacokinetic as well as pharmacodynamic characteristics of commonly used drugs and new drugs.This mini review focuses on the design, synthesis and pharmacological effects of several prodrugs and codrugs of the non-steroidal anti-inflammatory (NSAIDs), mefenamic acid. Exploitation of the prodrug approach has the potential to achieve a reduction of mefenamic acid GI (gastrointestinal) intolerance, enhance its bioavailability, mask its unpleasant sensation and prolong its duration of action. In addition, utilizing the prodrug concept might enhance the bioavailability of the counter partner drug of mefenamic acid codrug by increasing its lipophilicity.