Naproxcinod

Naproxcinod (nitronaproxen) is a nonsteroidal anti-inflammatory drug (NSAID) developed by the French pharmaceutical company NicOx. It is a derivative of naproxen with a nitroxybutyl ester to allow it to also act as a nitric oxide (NO) donor. This second mechanism of action makes naproxcinod the first in a new class of drugs, the cyclooxygenase inhibiting nitric oxide donators (CINODs), that are hoped to produce similar analgesic efficacy to traditional NSAIDs, but with less gastrointestinal and cardiovascular side effects. Naproxcinod (nitronaproxen) is a nonsteroidal anti-inflammatory drug (NSAID) developed by the French pharmaceutical company NicOx. It is a derivative of naproxen with a nitroxybutyl ester to allow it to also act as a nitric oxide (NO) donor. This second mechanism of action makes naproxcinod the first in a new class of drugs, the cyclooxygenase inhibiting nitric oxide donators (CINODs), that are hoped to produce similar analgesic efficacy to traditional NSAIDs, but with less gastrointestinal and cardiovascular side effects. On December 2006, Scientific American distinguished naproxcinod as one of the ten most promising treatments for the world's biggest health threats; however, in 2010 the U.S. Food and Drug Administration determined that further clinical trials would be needed to obtain approval. Many people are currently relying on traditional NSAIDs and COX-2 inhibitors (for example celecoxib) to treat chronic pain and inflammation. COX-2 inhibitors have been associated with an increased risk of serious cardiovascular events such as strokes or heart attacks. Therefore, there is an unmet need for safer medications. This need is particularly acute among patients with high cardiovascular risk like hypertension which represents 50% of osteoarthritis sufferers. Three phase III clinical trials led by NicOx have shown that naproxcinod was effective to treat pain against knee osteoarthritis and hip osteoarthrtis. A phase II study showed no significant differences in efficacy between naproxcinod and the COX-2 inhibitor rofecoxib in the treatment of pain. In osteoarthritis, a 750 mg dose is equipotent to 500 mg of naproxen for the treatment of inflammation but with the added benefit of attenuating the cardiovascular effects traditionally associated with NSAIDs. In July 2010 the FDA decided not to approve naproxcinod. Naproxcinoid is metabolized to naproxen and a nitric oxide donating moiety. NO has various cardiovascular effects, including vasodilatory and platelet-inhibitory actions as well as the inhibition of vascular smooth muscle proliferation that serves to maintain normal vascular tone. According to some experts, cardiovascular risks induced by COX-2 inhibitors are caused by increases in blood pressure. Naproxcinod demonstrated in a clinical trial with 916 patients to have a blood pressure profile similar to placebo. Two phase II randomized controlled trials have shown a decreased systolic blood pressure by 2.1 mmHg after patients took naproxcinod (375 mg or 750 mg twice daily) for six weeks. These effects were especially pronounced in hypertensive populations. During a U.S. Food and Drug Administration (FDA) COX-2 advisory committee meeting, doctors have underlined the important role of small increase in blood pressure. They cited the CAMELOT trial which has concluded that even a small decrease in systolic blood pressure of 5 mmHg could lead to a reduction of 31% in cardiovascular events. Clinical studies about rofecoxib have shown that this drug increases the systolic blood pressure.