Carbonic Anhydrase Inhibition by Flurbiprofen and Related Agents

Abstract

Flurbiprofen, a nonsteroidal anti-inflammatory drug (NSAID), reduces bone resoφtion in periodontal disease. This therapeutic effect has been attributed to inhibition of prostaglandin synthesis. In view of the importance of carbonic anhydrase (CA) in bone resoφtion, we examined the CA-inhibitory properties of flurbiprofen using bovine and human CA II and compared them with those of acetazolamide and two other NSAIDs, ibuprofen and indometacin. Flurbiprofen inhibited both human and bovine erythrocyte CA II but to a much lesser degree than acetazolamide. Ibuprofen and indometacin were much less active in inhibiting CA II than flurbiprofen.

Life‐threatening hypokalaemia associated with ibuprofen‐induced renal tubular acidosis

“…More recently, celecoxib and valdecoxib, which are COX‐2 selective NSAIDs, have been demonstrated to be potent inhibitors of CA due to binding of their sulfonamide moiety to its zinc (Zn 2+ ) ion 15 . Although ibuprofen lacks a sulfonamide moiety, it can inhibit human and bovine erythrocyte CA II 14 . CA inhibition would be consistent with our observations of both proximal and distal RTA.…”

“…Induction of these auto‐antibodies has resulted in the development of RTA in a mouse model of Sjögren syndrome 12 . Other NSAIDs including aspirin 13 and flurbiprofen 14 have been shown to have CA‐inhibitory activity in vitro. More recently, celecoxib and valdecoxib, which are COX‐2 selective NSAIDs, have been demonstrated to be potent inhibitors of CA due to binding of their sulfonamide moiety to its zinc (Zn 2+ ) ion 15 .…”

Hypokalaemia and Renal Tubular Acidosis due to Abuse of Nurofen Plus

“…Carbonic anhydrase (CA) exists as 15 isoforms and CA type two (CAII) is the predominant form (95%) in the kidney [8]. Deficiency of CAII has been demonstrated to cause renal tubular acidosis and nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to inhibit CAII actions, although the effects of Ibuprofen were less than flurbiprofen [9, 10]. This mechanism may explain why Ibuprofen toxicity has variously been described as causing type two or type four renal tubular acidosis as CAII is distributed throughout most of the nephron and therefore its inhibition may not cause solely a proximal tubular effect.…”

Impact of the Timing of Indomethacin Treatment in a Model of Synchronized Bone Remodelling in Rats

“…In fact loss of attachment of osteoclasts from their substrate induces cell apoptosis (Sakai et al 2000). Moreover in vitro, indomethacin inhibits carbonic anhydrase II, a key enzyme in osteoclast machinery (Greene et al 1992). Taken as a whole, these data strongly suggest that resorbing osteoclasts were disturbed by indomethacin treatment.…”