Enhanced analgesia and suppression of plasma beta-endorphin by the S(+)-isomer of ibuprofen. Analgesic efficacy of a hydrocodone with ibuprofen combination compared with ibuprofen alone for the treatment of acute postoperative pain. Multicenter clinical trial of ibuprofen and acetaminophen in the treatment of postoperative dental pain. Comparison of rofecoxib and celecoxib, two cyclooxygenase-2 inhibitors, in postoperative dental pain: a randomized, placebo- and active-comparator-controlled clinical trial. Ibuprofen arginate provides effective relief from postoperative dental pain with a more rapid onset of action than ibuprofen. Evaluation of different doses of soluble ibuprofen and ibuprofen tablets in postoperative dental pain. Comparison of the analgesic efficacy of concurrent ibuprofen and paracetamol with ibuprofen or paracetamol alone in the management of moderate to severe acute postoperative dental pain in adolescents and adults: a randomized, double-blind, placebo-controlled, parallel-group, single-dose, two-center, modified factorial study. A randomised, five-parallel-group, placebo-controlled trial comparing the efficacy and tolerability of analgesic combinations including a novel single-tablet combination of ibuprofen/paracetamol for postoperative dental pain. MK-0703 (a cyclooxygenase-2 inhibitor) in acute pain associated with dental surgery: a randomized, double-blind, placebo- and active comparator-controlled dose-ranging study. Comparative study of ibuprofen lysine and acetaminophen in patients with postoperative dental pain. Analgesic efficacy of bromfenac, ibuprofen, and aspirin in postoperative oral surgery pain.
Peripheral nociceptive barrage after tissue injury results in acute pain and a variety of physiologic responses, including pituitary secretion of beta-endorphin. This study evaluated whether administration of the pharmacologically active S(+)-isomer of ibuprofen suppresses acute pain and plasma beta-endorphin levels in the oral surgery model of acute pain.
                Subjects in a single-dose, double-blind, parallel-group study received either 200 mg S(+)-ibuprofen, 400 mg S(+)-ibuprofen, 400 mg racemic ibuprofen, or placebo. Both doses of S(+)-ibuprofen resulted in significantly greater analgesia over the first 60 minutes in comparison to racemic ibuprofen and placebo; the 400 mg dose of S(+)-ibuprofen also produced greater analgesia at 2 and 3 hours. Plasma levels of immunoreactive beta-endorphin decreased over time coincident with the onset of analgesia in all groups but were significantly less than placebo after both doses of S(+)-ibuprofen from 30 to 120 minutes.
                These findings show that, compared with racemic ibuprofen, administration of the S(+)-isomer of ibuprofen results in faster analgesic onset, greater peak analgesia, similar duration of action, and a low incidence of adverse effects, while suppressing nociceptive activation of the pituitary-adrenal axis. Hydrocodone is a semisynthetic opioid with analgesic and antitussive properties qualitatively similar to other opioid agonists. Ibuprofen is a nonsteroidal antiinflammatory agent with analgesic and antipyretic activity and is an effective, primarily peripheral-acting antiinflammatory analgesic. The objective of this clinical trial was to determine the additive analgesic effect of the combination of 15 mg hydrocodone bitartrate with 400 mg ibuprofen, relative to 400 mg ibuprofen alone and placebo, in the treatment of postoperative pain. The single-dose analgesic efficacy of the combination of hydrocodone bitartrate with ibuprofen was compared with ibuprofen alone and placebo in 120 patients with moderate or severe postoperative pain after abdominal surgery. Analgesia was measured during the 6-hour period after dosing based on onset of relief, hourly and summary variables, and duration of effect. A significantly greater proportion of patients treated with the hydrocodone/ibuprofen combination reported onset of relief compared with ibuprofen or placebo; however, the distribution functions for time to onset of relief did not differ among treatments. Hydrocodone with ibuprofen and ibuprofen alone were significantly more effective than placebo for all measures of analgesia. The combination of hydrocodone with ibuprofen was significantly superior to ibuprofen for all hourly analgesic evaluations, weighted sum of pain intensity differences (SPID), total pain relief (TOTPAR), and global rating of study medication. No patients in the hydrocodone with ibuprofen group required analgesic remedication during the 6-hour study period, compared with 25% and 82% in the ibuprofen and placebo groups, respectively. The analgesic superiority of 15 mg hydrocodone bitartrate combined with 400 mg ibuprofen compared with 400 mg ibuprofen alone was demonstrated across many efficacy variables. Pharmacological management of pain for acute and chronic conditions has been guided by a scientific understanding of peripheral and central acting mechanisms for the control of inflammation as well as pain. Oral surgery pain is a reliable model to reference the effectiveness of commonly used analgesics such as ibuprofen and acetaminophen. A total of 706 patients who were experiencing moderate to severe pain received a single dose of ibuprofen, acetaminophen, or placebo. After 6 hours, the degree of pain relief and tolerance was assessed. Ibuprofen has important implications for postoperative pain in clinical practice. Pain is a common complaint, often occurring in conjunction with inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used analgesic agents in ambulatory patients. In recent studies, the cyclooxygenase-2 (COX-2) inhibitor rofecoxib demonstrated analgesic effects similar to those of NSAIDs in the treatment of acute pain and primary dysmenorrhea. The present randomized, single-dose, double-blind, double-dummy, placebo- and active-comparator-controlled, parallel-group study was undertaken to compare the analgesic efficacy of the COX-2 inhibitors rofecoxib 50 mg and celecoxib 200 mg with that of ibuprofen 400 mg and placebo in patients with postoperative dental pain. Two hundred and seventy-two patients experiencing pain after the removal of > or =2 third molars were randomized according to pain severity (moderate vs severe) to receive a single dose of placebo (n = 45), rofecoxib 50 mg (n = 90), celecoxib 200 mg (n = 91), or ibuprofen 400 mg (n = 46). Using a patient diary, patients recorded pain intensity, pain relief, and global evaluations throughout the 24-hour period after dosing. The overall analgesic effect, onset of action, peak effect, and duration of effect were evaluated, with the primary end point being total pain relief over 8 hours (TOPAR8). The safety profile was assessed on the basis of physical findings, laboratory results, and spontaneous reports of adverse experiences. The results showed that compared with celecoxib, rofecoxib had superior analgesic effects on all measures of analgesic efficacy, including overall analgesic effect (TOPAR8, 18.3 vs. 12.5; P<0.001), time to onset of effect (30 vs. 60 minutes; P = 0.003), peak pain relief (score, 2.8 vs 2.3; P<0.05), and duration of effect (>24 vs. 5.1 hours; P<0.001). In addition, rofecoxib's analgesic efficacy was similar to that of ibuprofen (TOPAR8, 18.3 vs. 17.0; P = 0.460), but the duration was longer (P<0.05); with ibuprofen, the time to on set was 24 minutes, peak pain relief score was 2.9, and duration of analgesic effect was 8.9 hours. The safety profile was similar across all treatment groups. Thus rofecoxib provided analgesic efficacy superior to that of celecoxib and comparable to that of ibuprofen in the treatment of patients with acute postoperative dental pain. Ibuprofen is a safe and effective analgesic, but some formulations have a slow onset of action. Ibuprofen arginate is a rapidly absorbed salt designed to promote more rapid onset of analgesia. A clinical trial was conducted in 226 patients with postoperative dental pain to assess the analgesic efficacy and speed of onset of the arginine salt of ibuprofen compared with one of the commercially available forms of ibuprofen. Patients were administered a single dose of either ibuprofen arginate (200 mg or 400 mg), ibuprofen (200 mg or 400 mg), or placebo in this double-blind, randomized trial. To determine the onset of action of the study medication patients were required to note time to "any" pain relief and then time to "meaningful" pain relief, using the two-stopwatch method. Pain intensity and relief were assessed using traditional categorical scales over a 6-h period. Meaningful pain relief was achieved in 42 min and 24 min for ibuprofen arginate 200 mg and 400 mg, respectively, compared with 50 min and 48 min for ibuprofen 200 mg and 400 mg, respectively ( P<0.05). The results for the measurements of analgesic effectiveness [sum of pain intensity difference, total pain relief (TOTPAR), peak pain relief and overall evaluation of treatment] all showed that both doses of ibuprofen arginate and both doses of ibuprofen were significantly better than placebo and both 200-mg and 400-mg ibuprofen arginate doses were significantly better than ibuprofen 200 mg for peak pain relief. Mean plasma ibuprofen concentrations at 30 min and 60 min, respectively, were: ibuprofen arginine 200 mg, 13.9 micro g/ml and 15.7 micro g/ml; ibuprofen arginine 400 mg, 29.5 micro g/ml and 29.3 micro g/ml; ibuprofen 200 mg 2.5 micro g/ml and 5 micro g/ml; ibuprofen 400 mg, 2.3 micro g/ml and 7.4 micro g/ml. ( P<0.05). Adverse event profiles were similar across treatment groups. These results overall suggest that ibuprofen arginate when taken at doses equivalent to commercially available ibuprofen formulations produces analgesia that is faster in onset. The object of the study was to assess the comparative efficacy of three single doses (200, 400, 600 mg) of soluble ibuprofen and ibuprofen tablets after third molar surgery in 148 patients and aged 18-40 years. Outcome was measured by overall assessment of pain (AUC360) assessed from serial visual analogue scales, the number of patients taking additional analgesic and by overall assessment of medication evaluated on a five-point categorical scale. Over the 6-hour investigation period all the ibuprofen treatments with the exception of ibuprofen tablets 200 mg resulted in significantly less pain (p < 0.05) than placebo treatment. A large number of patients required additional analgesia during the investigation period, but the time to taking it was significantly earlier in the placebo group. No significant dose response (p > 0.05) was observed for either ibuprofen preparations assessed by the outcome variable of overall pain experience (AUC360) or time to additional analgesia. There was no significant difference in pain scores or time to taking additional analgesics between the respective doses of soluble and tablet formulations of ibuprofen. Both soluble and tablet formulations of ibuprofen provide effective pain control in the early postoperative period after removal of impacted third molars. There is little analgesic advantage in increasing the dose to 600 mg and only minimal benefit from using a soluble formulation of the drug. Combination analgesics may offer improved analgesic efficacy, particularly for moderate to severe pain.
                This study evaluated the analgesic benefits of concurrent ibuprofen and paracetamol compared with each drug used alone in the management of acute postoperative dental pain.
                Healthy patients aged 16 to 40 years undergoing surgical removal of 3 to 4 impacted molars (total impaction score > or = 9) were enrolled in this randomized, double-blind, placebo-controlled, parallel-group, single-dose, 2-center, modified factorial US study. Patients were randomly assigned in a ratio of 2:1:2:1:1 to ibuprofen 400 mg/paracetamol 1000 mg, ibuprofen 200 mg/paracetamol 500 mg, ibuprofen 400 mg, paracetamol 1000 mg, or placebo when postoperative pain reached moderate to severe intensity. The primary efficacy end point was the sum of pain relief and pain intensity differences from 0 to 8 hours (SPRID8). Several secondary end points were also measured, including total pain relief (TOTPAR), sum of pain intensity differences (SPID), and SPID on the visual analog scale (SPID VAS) at various time points. Other analgesic efficacy measures included peak effect, onset and duration of effect, and patients' overall assessment of treatment. The tolerability of study medications was assessed in terms of the frequency and nature of adverse events, which were assessed with standard questions, as well as changes from baseline in vital signs.
                A total of 234 patients were randomly assigned to treatment and included in the intent-to- treat population. The patients were predominantly female (74.4% [174/234]) and white (76.5% [179/234]); mean (SD) age was 20.8 (3.1) years and weight was 69.1 (16.5) kg. For SPRID8, the group treated with ibuprofen 400 mg/paracetamol 1000 mg had significantly better mean scores compared with ibuprofen alone (P < 0.001), paracetamol alone (P < 0.001), and ibuprofen 200 mg/paracetamol 500 mg (P = 0.02). The group taking ibuprofen 200 mg/paracetamol 500 mg achieved significantly better mean SPRID8 scores than paracetamol alone (P = 0.03), but not ibuprofen alone (P = NS). Ibuprofen 400 mg/paracetamol 1000 mg was associated with significantly better scores than was single-agent therapy for TOTPAR, SPID, and SPID VAS at all time intervals and for SPRID from 4 to 6 hours (all, P < 0.001). Pairwise comparisons found statistically significant differences in favor of all active treatments versus placebo for virtually all efficacy end points, thereby supporting assay sensitivity. Adverse events were similar across treatments; the most frequent were nausea (26.1% [61/234]), vomiting (18.8% [44/234]), headache (10.3% [24/234]), and dizziness (8.1% [19/234]).
                Concurrent ibuprofen and paracetamol appeared to provide significantly better analgesic efficacy compared with ibuprofen or paracetamol alone for acute postoperative dental pain in these adolescents and adults.
                Copyright 2010 Excerpta Medica Inc. All rights reserved. Combination analgesia is often recommended for the relief of severe pain. This was a double-blind, 5-arm, parallel-group, placebo-controlled, randomised, single-dose study designed to compare the efficacy and tolerability of a novel single-tablet combination of ibuprofen and paracetamol with that of an ibuprofen/codeine combination, and a paracetamol/codeine combination, using the dental impaction pain model. Subjects with at least 3 impacted third molars and experiencing moderate to severe postoperative pain were randomised to receive: 1 or 2 tablets of a single-tablet combination of ibuprofen 200mg/paracetamol 500mg; 2 tablets of ibuprofen 200 mg/codeine 12.8mg; 2 tablets of paracetamol 500mg/codeine 15mg; or placebo. Results for the primary endpoint, the sum of the mean scores of pain relief combined with pain intensity differences over 12hours, demonstrated that 1 and 2 tablets of the single-tablet combination of ibuprofen/paracetamol were statistically significantly more efficacious than 2 tablets of placebo (P<0.0001) and paracetamol/codeine (P⩽0.0001); furthermore, 2 tablets offered significantly superior pain relief to ibuprofen/codeine (P=0.0001), and 1 tablet was found noninferior to this combination. Adverse events were uncommon during this study and treatment emergent adverse events were statistically significantly less frequent in the groups taking the ibuprofen/paracetamol combination compared with codeine combinations. In conclusion, 1 or 2 tablets of a single-tablet combination of ibuprofen 200mg/paracetamol 500mg provided highly effective analgesia that was comparable with, or superior to, other combination analgesics currently indicated for strong pain. A single-tablet combination of ibuprofen 200mg/paracetamol 500mg provides highly effective analgesia, comparable or superior to other combination analgesics indicated for strong pain.
                Copyright © 2011. Published by Elsevier B.V. MK-0703 is a selective cyclooxygenase-2 inhibitor investigated for the treatment of acute pain and inflammation. The purpose of this single-dose, randomized, double-blind, double-dummy, placebo-controlled, parallel-group study was to compare MK-0703 12.5, 50, and 100 mg with ibuprofen 400 mg or placebo in patients who experienced moderate to severe pain after surgical removal of at least 2 third molars. Overall analgesic effect, duration of analgesic effect, time to onset of analgesic effect, peak analgesic effect, and tolerability were assessed over a 24-hour postdose period. The primary endpoint of this study was total pain relief over 8 hours postdose. The study included 121 patients (mean age, 23 yr); 16, 31, 28, 31, and 15 patients enrolled in the placebo, MK-0703 12.5 mg, MK-0703 50 mg, MK-0703 100 mg, and ibuprofen 400 mg groups, respectively. Both MK-0703 50 and 100 mg were significantly more effective than placebo for all endpoints (P < 0.01) and comparable with ibuprofen 400 mg. The onset of analgesic effect in the MK-0703 50 mg and 100 mg and ibuprofen 400 mg groups did not differ significantly from each other (P > 0.20). MK-0703 was generally well tolerated in single doses up to 100 mg. In summary, MK-0703 50 and 100 mg were efficacious in the treatment of postoperative dental pain and were indistinguishable from the active comparator, ibuprofen 400 mg. This single-dose, double-blind, parallel-group, single-site study compared ibuprofen lysine 400 mg with acetaminophen 1000 mg and placebo in 240 patients with moderate-to-severe postoperative dental pain. The relative onset of analgesic response, overall analgesic efficacy, duration of effect, and safety were assessed over a 6-hour postdose period. Analgesic efficacy was assessed by patient self-rating of pain intensity, pain relief, time to meaningful pain relief, need for additional analgesic medication, and patient global evaluation. Both ibuprofen lysine 400 mg and acetaminophen 1000 mg were significantly (P < or = 0.05) more effective than placebo. Ibuprofen lysine had a significantly (P < or = 0.05) faster onset of action with greater peak and overall analgesic effect than did effect than did acetaminophen. All treatments were generally well tolerated. We recently demonstrated that 25 mg of bromfenac, a new nonsteroidal anti-inflammatory analgesic, is at least as effective as 400 mg of ibuprofen in relieving postoperative oral surgery pain. Our objective in this study was to determine whether higher doses were significantly more effective. Two hundred eighty (280) outpatients with postoperative pain after the surgical removal of impacted third molars were randomly assigned, on a double-blind basis, a single oral dose of 10, 25, 50, or 100 mg bromfenac; 650 mg aspirin; 400 mg ibuprofen; or placebo. Subjects rated their pain and its relief for 8 hours. All active treatments were significantly superior to placebo, and bromfenac and ibuprofen were significantly superior to aspirin. The slope of the dose-response curve of bromfenac was significant. The 100 mg bromfenac dose was significantly more effective than the 400 mg ibuprofen dose and had a significantly longer duration of analgesic action.
The information from the single trial in acute postoperative pain suggests it to be a useful analgesic, but at doses not very different from racemic ibuprofen.