PARECOXIB NA

Parecoxib sodium is an injectable COX-2 inhibitor, launched as an anti-inflammatory agent and for the management of acute pain. Parecoxib is an amide prodrug of Pharmacia’s valdecoxib. It can be administered by either i.m. or i.v. routes, in contrast to other currently available COX-2 inhibitors which are poorly watersoluble. Parecoxib sodium can be prepared from valdecoxib by acylation of the sulfonamide with propionic anhydride. Parecoxib sodium exhibited potent acute and chronic antiinflammatory activity in rats, as demonstrated in the carrageenan air pouch model, where 98% of inhibition was achieved with the dose of 0.3mg/kg, and in the adjuvant arthritis model (ED₅₀ = 0.08mglkg). Moreover, in the carrageenan footpad edema model, parecoxib sodium showed excellent efficacy (ED₅₀ = Smglkg) and a rapid onset of action comparable with the most potent analgesic ketorolac. In this model, it produced a complete blockade of the carrageenan-induced hyperalgesia within 1 h after iv. administration. Pharmacokinetic studies indicated that parecoxib sodium completely and rapidly converted in valdecoxib with bioequivalence found between parenterally administered parecoxib sodium and orally administered valdecoxib. The maximum plasma concentrations of valdecoxib were 2530% greater after iv. than i.m. administration of parecoxib and tnax was respectively 0.5 h after iv. and 1.5 h after i.m. administration. Parecoxib sodium had greater gastrointestinal tolerance than ketorolac and had no significant effect on platelet aggregation. Parecoxib sodium was as effective as ketorolac or even superior to morphine and placebo in the treatment of severe pain (such as that observed following gynaecologic or orthopaedic surgery). Mean times to rescue medication were longer with parecoxib compared to morphine. Parecoxib sodium works 12-14 min after i.v. administration and a dose of 40 mg provides good or excellent relief of pain in approximately 90% of patients. Thus, parecoxib sodium is a non-narcotic, specific COX-2 inhibitor, which provides potent analgesic ability and fulfils some important requirements for the pain management in the post-operative period such as i.v. formulation, rapidity of action, and short half-life. Furthermore, although valdecoxib is a substrate for CYP3A4 as other drugs used in the perioperative period, it does not interfere either with the metabolism of the sedative/tranquilizer, midazolam, or with the intravenous anesthetic propofol.

Pharmacia (Searle) (USA)

Anti-inflammatory; analgesic (cyclooxygenase).

Dynastat