Description
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.
