Stephen A. Cooper

Single dose and multidose analgesic study of ibuprofen and meclofenamate sodium after third molar surgery

The purpose of this study was to compare the analgesic efficacy and safety of meclofenamate sodium with ibuprofen after dental impaction surgery. This study was double-blind and used a unique methodology. Patients (N = 254) were first randomized into the single dose phase of the study that included placebo, meclofenamate 50 mg, meclofenamate 100 mg, ibuprofen 200 mg, and ibuprofen 400 mg, followed by a 7-day multidose phase in which patients in the placebo group were rerandomized into one of the active treatment cells. In the single dose phase, all active treatments were significantly more efficacious than placebo for every summary analgesic measure. A positive dose-response was seen for both active drugs with meclofenamate 100 mg and ibuprofen 400 mg exhibiting the greatest efficacy for pain relief, pain reduction, time to remedication, and overall evaluation. Side effects were reported by 26 patients. They were evenly distributed among treatment groups with headache and drowsiness being the most common. During the multidose phase, there were only small differences in efficacy measures among active treatment groups. However, meclofenamate produced a higher incidence of stomach cramps and diarrhea than did ibuprofen (8.8% and 7.2% versus 0.8% and 0.8%). This study indicates that higher doses of nonsteroidal anti-inflammatory drugs are most effective immediately after surgery and that lower doses of these drugs can be used after the first postoperative day. The side effect profile of nonsteroidal anti-inflammatory analgesics is best observed with the use of a multidose study design.

Bromfenac sodium, acetaminophen/oxycodone, ibuprofen, and placebo for relief postoperative pain

The objective of this double-masked, parallel-group, multicenter, inpatient study was to compare bromfenac with an acetaminophen/oxycodone combination and ibuprofen in patients who had pain due to abdominal gynecologic surgery. In the 8-hour, single-dose phase, 238 patients received single oral doses of bromfenac (50 or 100 mg), acetaminophen 650 mg/oxycodone 10 mg, ibuprofen 400 mg, or placebo. In the multiple-dose phase, 204 patients received bromfenac, acetaminophen/oxycodone, or ibuprofen for up to 5 days. In the single-dose phase, both bromfenac doses produced peak analgesic responses equivalent to acetaminophen/oxycodone, but the responses to bromfenac were longer lasting. Bromfenac produced significantly better overall (8-hour) analgesic summed scores than acetaminophen/oxycodone. Ibuprofen was less efficacious than the other analgesics. The remedication rate was lower in both bromfenac groups than in the other treatment groups. The acetaminophen/oxycodone group reported more somnolence and vomiting. Single doses of bromfenac provided analgesia at least equivalent to that of the acetaminophen/oxycodone combination, with a longer duration of action. Both doses of bromfenac and acetaminophen/oxycodone were superior to ibuprofen in this study.

Narcotic receptor blockade and its effect on the analgesic response to placebo and ibuprofen after oral surgery.

The purpose of this study was to evaluate the contribution of endogenous opiates to the analgesic response after treatment with placebo, codeine, and ibuprofen after oral surgery. Eighty-one patients undergoing complicated dental extractions were pretreated with either a placebo or the narcotic antagonist naltrexone 50 mg, 30 minutes before surgery. After surgery, patients self administered one of three possible postsurgical medications, which included placebo, codeine 60 mg, and ibuprofen 400 mg, when their pain reached a moderate or severe intensity. The study was double-blind with the three postsurgical treatments being randomly allocated within each presurgical treatment block. Pain intensity, pain relief, pain half gone, and overall evaluations were assessed for up to 6 hours. Ibuprofen was significantly more efficacious (p < .05) than codeine or placebo for most analgesic measures. The administration of naltrexone before surgery reduced the analgesic response to both placebo and codeine. Pretreatment with naltrexone did not diminish the peak analgesic response to ibuprofen, but surprisingly prolonged (p < .05) the duration of its action. The results suggest that a blockade of endogenous opiates by naltrexone diminished the placebo response, but that naltrexone may prolong ibuprofen analgesia by some unknown mechanism.

The Analgesic Interaction of Misoprostol with Nonsteroidal Anti-Inflammatory Drugs.

The purpose of this project was to evaluate the analgesic efficacy of misoprostol when combined with ibuprofen or diclofenac Na. Animal experiments using the inflamed rat paw formalin model suggested that misoprostol potentiates the analgesic effect of some NSAIDs (nonsteroidal anti-inflammatory drugs) including diclofenac Na but not propionic acid derivatives or opiates. The dental pain model was used to evaluate the clinical relevance of this interaction. Patients received a single oral dose of study medication following surgical removal of impacted teeth. Patients were medicated for moderate to severe postsurgical pain and then filled in an analgesic diary for a 6-h observation period. Several blood samples were taken over the observation period. In addition, microdialysis samples were taken directly from the extraction socket and were analyzed for immunoreactive prostaglandin E(2) levels. The studies were single-dose, parallel group and double-blind assays. In the first study, 70 patients received an oral dose of either placebo (n = 13), misoprostol 200 &mgr;g (n = 18), ibuprofen 200 mg (n = 19), or the combination of misoprostol + ibuprofen (n = 20). Misoprostol alone demonstrated a small analgesic effect compared to placebo. Both the ibuprofen and combination groups were substantially more effective than placebo but not different from each other. The combination group had higher ibuprofen blood levels during the first 45 min but had a lower C(max) and longer time to T(max). The second study evaluated oral doses of placebo (n = 11), misoprostol 200 &mgr;g (n = 21), diclofenac Na 50 mg (n = 18), and the combination of misoprostol + diclofenac Na (n = 20). Relative to placebo, misoprostol performance was similar to the first study. When the results of the two studies were combined, there was a small, but statistically significant, analgesic effect for misoprostol. Diclofenac Na was superior to both placebo and to misoprostol alone. The combination was the most effective treatment, and for hours 4--6 it was significantly better than diclofenac Na alone. Analysis of the blood samples showed an earlier and higher peak effect for the diclofenac Na group compared to the combination, and the combination again had a lower C(max). The microdialysis probe assays demonstrated that misoprostol depressed PGE(2) levels at the peripheral site of trauma over the first 2 h after surgery. These pilot studies used small samples, and the results only suggest trend effects. Both studies demonstrated that misoprostol 200 &mgr;g, a prostaglandin analog, does have an analgesic effect. When combined with ibuprofen, there was no potentiation of analgesia. In contrast, the combination of misoprostol + diclofenac Na demonstrated an enhanced peak effect, total effect for pain intensity difference and pain relief (sum pain intensity difference [SPID] and total pain relief [TOTPAR]), and

Picenadol in a large multicenter dental pain study.

Study Objective. To estimate the analgesic dose of picenadol hydrochloride equal to codeine 60 mg in a dental pain model.

Altered pharmacokinetics of ibuprofen enantiomers caused by dental surgery

Clinical Pharmacology & Therapeutics (1996) 59, 217–217; doi: 10.1038/sj.clpt.1996.366

Absorption Kinetics of Diclofenac in Dental Patients After Molar Extraction

Clinical Pharmacology & Therapeutics (1996) 59, 204–204; doi: 10.1038/sj.clpt.1996.314