Clinical pharmacology of etoricoxib: a novel selective COX2 inhibitor.
The development of COX2 inhibitors with improved biochemical selectivity (such as etoricoxib and valdecoxib) over that of commercially available coxibs has been driven by the potential advantage of safety using higher coxib doses for increased efficacy. Etoricoxib has been approved in the UK as a once-daily medicine for symptomatic relief in the treatment of osteoarthritis (OA), rheumatoid arthritis (RA) and acute gouty arthritis. It is currently approved with additional indications (i.e., for relief of acute pain associated with dental surgery, for primary dysmenorrhoea and for chronic musculo-skeletal pain, including chronic lower-back pain) in Mexico, Brazil and Peru. Etoricoxib has an in vitro COX1/COX2 IC(50) ratio of 344, the highest of any coxib. The administration of therapeutic doses of etoricoxib to healthy subjects does not affect COX1 activity in circulating platelets and gastric biopsies. The profound inhibition of monocyte COX2 activity at 24 h after dosing, as predicted by a pharmacological half-life of approximately 22 h, supports a once-daily dosing regimen of etoricoxib. In randomised, well-controlled clinical trials, etoricoxib has been shown to have a comparable clinical efficacy with traditional NSAIDs. Combined analysis of efficacy trials with etoricoxib versus non-selective NSAIDs has shown that the drug halves both investigator-reported upper gastrointestinal perforation, ulcers and bleeds (PUBs) and confirmed PUBs, and reduces the need for gastroprotective agents and gastrointestinal comedications by approximately 40%. The risk of lower extremity oedema and hypertension adverse experiences with etoricoxib was low and generally similar to comparator NSAIDs in a combined analysis of eight Phase III studies in OA, RA, chronic low-back pain and surveillance endoscopy. Large, randomised clinical trials have been planned to confirm the renal, gastrointestinal and cardiovascular safety of etoricoxib.
Patrignani
Paola
P
Sezione di Farmacologia, Dipartimento di Medicina e Scienze dell'Invecchiamento, Università di Chieti G. D'Annunzio, c/o Palazzina delle Scuole di Specializzazione, Via dei Vestini 31, 66013 Chieti, Italy. ppatrignani@unich.it
Capone
Marta L
ML
Tacconelli
Stefania
S
D015210:Arthritis, Gouty / Q000188:drug therapy; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D002319:Cardiovascular System / Q000187:drug effects; D002986:Clinical Trials as Topic; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000077613:Etoricoxib; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D017116:Low Back Pain / Q000188:drug therapy; D008565:Membrane Proteins; D010003:Osteoarthritis / Q000188:drug therapy; D010149:Postoperative Pain / Q000188:drug therapy; D011451:Prostaglandin-Endoperoxide Synthases; D011725:Pyridines / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D013450:Sulfones / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011725:Pyridines; D013450:Sulfones; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000077613:Etoricoxib