Anti-inflammatory agent - naproxcinod
The demise of COX-2 inhibitors has left a gaping hole in the armoury of painkillers. Designed to avoid the potentially severe gastric side-effects of earlier NSAIDs such as ibuprofen and naproxen, in a very few cases they were shown to have cardiac side-effects.
The demise of COX-2 inhibitors has left a gaping hole in the armoury of painkillers. Designed to avoid the potentially severe gastric side-effects of earlier NSAIDs such as ibuprofen and naproxen, in a very few cases they were shown to have cardiac side-effects.
There is thus a great need for new NSAIDs that are easier on the stomach, and the naproxen derivative naproxcinod, being developed by NicOX, fits this bill.1 As well a COX inhibitor it is also a nitric oxide donor, which has the effect of lowering the blood pressure and so may be useful in patients with a history of heart disease.
In a double blind, placebo-controlled Phase II trial, 970 patients with osteoarthritis in the hip or knee were given 750mg naproxcinod, 500mg of naproxen or placebo twice a day for six weeks.2 Those given naproxcinod had a 40% lower incidence of gastric and duodenal ulcers, at 9.7%, than those who took naproxen, whereas none of those given placebo developed ulcers. The two drugs were equivalent in their analgesic effects.
It has also been shown that the drug does not increase blood pressure. In an escalating dose trial in 118 patients, subjects were given either naproxcinod or naproxen, with doses of the former at 375, 750 and then 1125mg twice a day, or a similar regime with the latter of 250, 500 and 750mg twice a day.3 The 24-hour ambulatory blood pressure was measured at the start of the trial and before each dose escalation. At each dosage level, blood pressure was lower with naproxcinod than with naproxen: naproxcinod lowered it by an average of 2.3mmHg whereas naproxen increased it by an average of 1.5mmHg. This implies that naproxcinod is able to prevent the common NSAID side-effect of hypertension.
A further, larger scale trial gave similar results, and also showed a reduction in blood pressure in those also taking antihypertensives.4 Phase III trials are underway; but as it does still have gastric side-effects - albeit lower than with traditional NSAIDS - concomitant administration of a proton pump inhibitor is likely to be necessary.
Reference:
1. S. Fiorucci et al. J. Pharmacol. Exp. Ther. 2004, 311, 1264
2. L.S. Lohmander et al. Ann. Rheum. Dis. 2005, 64, 449
3. T.J. Schnitzer et al. Arth. Rheum. 2005, 53, 827
4. W.B. White et al. Am. J. Cardiol. 2009, 104, 840