Antiarthritic - cimicoxib
COX-2 inhibitors hit the headlines recently with the withdrawal of Merck's rofecoxib (Vioxx) due to increased the risk of cardiovascular side effects.
COX-2 inhibitors hit the headlines recently with the withdrawal of Merck's rofecoxib (Vioxx) due to increased the risk of cardiovascular side effects.
However, this appears not to be a general problem across the class, and research into new COX-2 inhibitors continues.
The principle behind the COX-2 inhibitors is to avoid the gastrointestinal side effects that can occur with non-steroidal anti-inflammatory drugs. All NSAIDs inhibit the enzyme cyclooxygenase, an essential component of the biosynthesis of the prostaglandins that cause pain and inflammation. The downside is that these prostaglandins also have a gastroprotective effect. The discovery that cyclooxygenase exists in two forms - COX-1, which has the beneficial effects, and COX-2, which is largely responsible for the adverse effects, led to the introduction of a new class of NSAIDs, the COX-2 inhibitors.
One such experimental drug is cimicoxib, being investigated by Spanish company Uriach.1 In a double blind randomised trial in healthy volunteers, controlled against both placebo and rofecoxib, the drug was given in single oral doses ranging from 3mg to 600mg, in comparison to placebo or 25mg rofecoxib.2 All doses of cimicoxib were safe and well tolerated, and 25mg cimecoxib had a similar effect to 25mg rofecoxib.
A similar Phase I trial was carried out in healthy volunteers. Subject were given either single or 12 doses of 25 or 100mg of cimicoxib, placebo, or 25mg rofecoxib once a day. Cimicoxib caused no adverse events, the lower dose had a similar effect to the doses of rofecoxib, and the higher dose had an increased effect in the inhibition of COX-2.
In a double blind randomised Phase II trial, 251 patients suffering from moderate to severe pain after the removal of impacted wisdom teeth were given 50, 100 or 200mg cimicoxib, 50mg rofecoxib or placebo. The two higher doses of cimicoxib were more effective than placebo, and the two 50mg doses gave comparable effects, but the onset of analgesia was much faster with cimicoxib. As a result of these positive findings, trials continue.