A double-blind, randomized comparison of intramuscularly and intravenously administered parecoxib sodium versus ketorolac and placebo in a post-oral surgery pain model.

BACKGROUND: Parecoxib sodium is an injectable cyclooxygenase-2-specific inhibitor developed for the treatment of acute pain. The analgesic efficacy of IV and IM parecoxib has been demonstrated in previous pilot studies using the post-oral surgery pain model. OBJECTIVE: This study was conducted to characterize the analgesic efficacy of parecoxib in healthy adults after oral surgery while comparing the efficacy and tolerability of the IV and IM routes of administration. METHODS: This was a double-blind, randomized, parallel-group, placebo- and active-controlled, single-dose, single-center trial. Patients experiencing moderate to severe post-operative pain after the extraction of > or =2 impacted third molars were randomized to receive parecoxib sodium 20 mg IM, 20 mg IV, 40 mg IM, or 40 mg IV; ketorolac tromethamine 60 mg IM; or placebo. Patients assessed pain intensity and pain relief (PR) at baseline and at designated intervals for 24 hours after administration of study medication or until rescue medication was taken. Analgesic efficacy was assessed in terms of time-specific pain intensity difference (PID) and PR, time to onset of analgesia, and time to use of rescue medication. RESULTS: Three hundred four patients were randomized to treatment. Parecoxib sodium 20 and 40 mg IM or IV and ketorolac 60 mg IM were significantly superior to placebo in PID, PR, time to onset of analgesia, and time to use of rescue medication (P < or = 0.05). Equal IV and IM doses of parecoxib were comparable on these measures; however, time to use of rescue medication was longer with IM compared with IV administration. Both doses of parecoxib were comparable to ketorolac 60 mg IM in time to onset of analgesia, but parecoxib 40 mg had a significantly longer duration of action (P < or = 0.05). The few statistically significant differences in PID and PR between parecoxib 40 mg and ketorolac favored ketorolac versus parecoxib 40 mg IV at earlier time points and parecoxib 40 mg IM versus ketorolac at later time points (P < or = 0.05). All treatments were well tolerated. CONCLUSIONS: Parecoxib IV and IM provided effective analgesia. The 40-mg dose was comparable to ketorolac 60 mg on most measures of analgesia but had a longer duration of action.

The injectable cyclooxygenase-2-specific inhibitor parecoxib sodium has analgesic efficacy when administered preoperatively.

Preoperative administration of analgesics may prevent or reduce hyperalgesia and inhibit inflammation and pain by reducing the synthesis of prostaglandins in response to surgical injury. We evaluated in this placebo-controlled study the analgesic efficacy and safety of single doses of parecoxib sodium (20, 40, and 80 mg IV) when administered before oral surgery. Efficacy assessments were recorded during the 24-h period after completion of surgery. All doses of parecoxib sodium were consistently and significantly superior to placebo as measured by time to rescue medication, proportion of patients requiring rescue medication, patient's global assessment, and pain intensity. There were no significant differences between the Parecoxib Sodium 40- and 80-mg groups, suggesting that the analgesic effect of preoperatively administered parecoxib sodium reaches a plateau at 40 mg in this model. Forty-eight percent of the Parecoxib Sodium 40-mg group required rescue medication in the 24-h study period, compared with 93% of patients in the Placebo group. Overall, there were fewer adverse events in parecoxib sodium-treated patients compared with placebo. These findings suggest that preoperative administration of parecoxib sodium, the injectable prodrug of the cyclooxygenase-2 specific inhibitor valdecoxib, is effective, safe, and well tolerated for treating postoperative pain.