RENAL TOXICITY OF THE SELECTIVE CYCLOOXYGENASE-2 INHIBITORS: CELECOXIB ANO ROFECOXIB

Abstract

Se/ective cyclooxygenase-2 inhibitors were deve!oped to avoid side effects of conventiona! non-steroidal anti-inflammatory drugs, including gastrintestina! and renal toxicity. However, recent studies have demonstrated that cyclooxygenase-2 is constitutively expressed in the kidney and is highly regu!ated in response to alterations in intravascular volume. When b!ood volume is compromised, the prostag!andins derived from cyclooxygenase-2, perform an important role in the renal circu!ation. Therefore, drugs that selectively inhibit cyclooxygenase-2 might be expected to produce effects on renal function similar to non-steroidal anti-inflammatory drugs, which inhibit both cyclooxygense-1 and cyc!ooxygenase-2. This review has the objective to assess the nephrotoxicity of the most recent generations of se/ective inhibitors of cyclooxygenase-2, named coxibs, emphasizing ce/ecoxib and rofecoxib, when they are administrated to individuais without previous renal impairment, as we/I as to those with renal failure. The publications in nationa! and international periodicals from 1999 to 2004, constituted the sample of analysis. This review has shown that se/ective cyclooxygenase-2 inhibitors, such as non-steroidal anti-inflammatory drugs, reduce sodium, potassium and water excretion, causing mi/d to modest increases in blood pressure and edema, and may cause, as we/1, acute renal failure in patients whose maintenance of adequate renal perfusion is "prostaglandin­ dependen t". ln individuais whose such maintenance happens by other mechanisms, those parameter alterations, whenever they occur, are generally transitional. The conclusion was that, the selective cyclooxygenase-2 inhibitors don't have higher renal safety than other non-steroidal anti-inflammatory drugs and, like them, must be used either cautiously ar not at ai/ in patients with predisposing diseases.