Effective nonsteroidal anti-inflammatory drugs devoid of gastrointestinal side effects: do they really exist?

Abstract

All nonsteroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal (GI) side effects. One focus of development was to design new drugs with reduced propensity for GI damage. With aspirin as the prototype, research efforts to develop NSAIDs with the efficacy but not the gastroduodenal damaging effects of aspirin have been partially successful. Techniques used to minimize gastric irritant potential include developing new drug classes, enteric coatings, nonacidic drugs, and prodrugs. Properties associated with the mucosal damaging effects of NSAIDs (potent inhibition of prostaglandin synthesis, solubility at low pH, and acid characteristic) are not found in the newer prodrugs such as droxicam and nabumetone. Droxicam was developed as a prodrug of piroxicam with equal efficacy, in addition to improved GI tolerance. Prodrugs may offer new molecules with pharmacological profiles and efficacy to toxicity ratios more acceptable to clinicians and patients alike.