Effects of Celecoxib and Diclofenac on Blood Pressure, Renal Function, and Vasoactive Prostanoids in Young and Elderly Subjects

Abstract

Cyclooxygenase (COX) inhibitors are among the most widely used drugs, especially in the elderly. It has been claimed that the new COX-2 inhibitors offer advantages in terms of drug safety. To test this hypothesis, the authors compared in a double-blind, randomized trial the effects of celecoxib (200 mg bid) and diclofenac (75 mg bid) on blood pressure and renal function in two groups (each n = 12) of young (mean age = 32 years) and elderly (mean age = 68 years) normotensive subjects. Changes from baseline in the 24-hour blood pressure profiles, parameters of the renin-angiotensin-aldosterone system, inulin clearance, urinary marker proteins, and eicosanoid excretion were monitored during the treatment period of 2 weeks. Comparison between celecoxib and diclofenac showed no significant difference in minor alterations of blood pressure. During daytime, there was a trend to elevation of mean arterial blood pressure (mmHg) by celecoxib in the elderly of 2.8 (95 % confidence interval [CI) = -2.5 to 8.2) in comparison with the young subjects of -1.3 (95% CI= -3.7 to 1.0); there was also a trend to elevation of mean arterial blood pressure by diclofenac in the elderly of 4.1 (95% CI= -1.2 to 9.4) in comparison with the young subjects of 0.4 (95% CI= -2.4 to 3.2). In both populations, the authors found no significant drug effects on the parameters of the renin-angiotensin-aldosterone system, inulin clearance, and urinary marker proteins. As expected, diclofenac reduced excretion of allprostanoids, whereas celecoxib did not affect production of TxB2 and its metabolites. Neither in young nor in elderly normotensive subjects were blood pressure and renal function significantly affected by a short-term treatment with standard doses of celecoxib and diclofenac. Therefore, normal aging appears not to represent a special risk factor in therapy with these two agents.

Effects of specific COX-2-inhibition on renin release and renal and systemic prostanoid synthesis in healthy volunteers

“…However, we observed a strong, but nonsignificant, trend toward reduction of urinary PGE-M excretion by celecoxib before (−14% in 24-hour urine and −34% in 2-hour urine) and after furosemide (−33%). In line with these results are the findings of Dilger et al [31], who reported a 35% reduction of urinary PGE-M excretion in young healthy volunteers treated for 15 days with celecoxib 200 mg twice a day. In contrast, the recently published study by Murphey et al [36] found a 62% reduction of urinary PGE-M excretion in healthy volunteers treated with rofecoxib 50 mg/day for 4 days.…”

“…Remarkably, in women older than 65 years with physiologic decline of renal function, sustained decreases of urinary PGE 2 excretion after administration of celecoxib 200 mg twice a day and naproxen 500 mg twice a day for 5 days were observed [30]. Two further studies which assessed the effect of flosulide [11] and celecoxib [31] on urinary PGE 2 excretion included male volunteers, resulting in high and varying PGE 2 excretion rates due to contamination of urine with seminal fluid. Similarly, the study by Kammerl et al [13] included male volunteers and reported only the combined excretion of PGE-M and PGE 2 .…”

Maternal nutrient restriction alters renal development and blood pressure regulation of the offspring

“…COX expression and its relationship with blood pressure have been widely investigated and meta-analyses of these results have found that COX inhibitors elevate blood pressure (Pope et al 1993;Johnson et al 1994). This finding has not been supported by more recent studies (Catella-Lawson et al 1999;Dilger et al 2002;Gertz et al 2002), and in the study of Pope et al (1993) raised blood pressure was found only in those animals that were hypertensive before the administration of the inhibitors. The increase in COX-2 expression in the animals from the present rat model, coupled with their reduced blood pressure, would support a role for COX in blood pressure regulation.…”

Pain and Its Treatment in Urology

“…The NSA has to be replaced by paracetamol in case of deterioration of renal function. Even in elderly patients NSA can be recommended as fi rst-line therapy, as Dil-ger et al [27] could not show any deterioration in blood pressure and renal function compared with young subjects.…”