The amphiprotic character of azapropazone and its relevance to the gastric mucosa

Abstract

Since most non-steroidal anti-inflammatory drugs (NSAIDs) contain only one obvious ionisable group at physiological pH levels then they may be easily identified as having either acidic or basic character. Basic NSAIDs are simply non-acidic NSAIDs capable of accepting a proton within the physiological pH range. Within this range, however, a few NSAIDs contain two obvious ionisable groups, one acidic and the other basic. Such compounds should be described as amphiprotic, and include NSAIDs such as 4- and 5-amino substituted salicylic acids, niflumic acid, amfenac, WY 18251, and azapropazone. The aqueous ionisation equilibrium of such compounds is complex and is described by two macroscopic ionisation constants. Evidence has accumulated during the last decade to support the view that the pharmacokinetic behaviour of NSAIDs contributes not only decisively to their therapeutic effects but also to the type and incidence of their side-effects.A priori, using a physico-chemical argument, certain amphiprotic NSAIDs should be better tolerated by the gastric mucosa than the classical acidic compound. Of those NSAIDs commercially available in the United Kingdom azapropazone remains the only one for which amphiprotic behaviour has been described. Following our examination of available data for azapropazone we conclude that the use of amphiprotic compounds represents a logical approach towards solving the problem of NSAID-induced gastric mucosal damage.