The analgesic efficacy of suprofen in periodontal and oral surgical pain

Suprofen is a new, orally effective nonsteroidal antiinflammatory analgesic of the propionic acid chemical class. Three separate single-dose studies were performed to evaluate the efficacy of suprofen in acute pain associated with periodontal surgery and removal of impacted third molars. Study medications were: A--suprofen 200 mg, codeine 60 mg, propoxyphene HCl 65 mg, and placebo; B--suprofen 400 mg and 200 mg, aspirin 650 mg, and placebo; C--suprofen 400 mg and 200 mg, aspirin 650 mg with codeine 60 mg, aspirin 650 mg alone, and placebo. Analgesic and side effect data were collected over a 6-hour period after patients medicated for moderate to severe pain. All studies were randomized, double-blinded, and parallel-group in design. Suprofen was significantly more effective than codeine 60 mg, propoxyphene HCl 65 mg, and aspirin 650 mg. Suprofen 400 mg appeared to be clinically more effective than the aspirin-codeine combination and the difference was statistically significant for most of the analgesic variables. Of the 224 patients who received suprofen in the 3 studies, 16 reported drowsiness and 1 reported constipation.     

Efficacy of disintegrating aspirin in two different models for acute mild-to-moderate pain: sore throat pain and dental pain

A recently developed fast-release aspirin tablet formulation has been evaluated in two different pain models. The dental impaction pain model and the sore throat pain model are widely used for assessing analgesia, including acute mild-to-moderate pain. Both studies were double-blind, randomized, parallel group and compared a single dose of 1000 mg aspirin with 1000 mg paracetamol and with placebo and investigated the onset and overall time course of pain relief. Speed of onset was measured by the double-stopwatch method for time to meaningful pain relief and time to first perceptible pain relief. Pain intensity and pain relief were rated subjectively over a 6-h (dental pain) and 2-h (sore throat pain) time period. In both models fast-release aspirin and commercial paracetamol were statistically significantly different from placebo for onset of action, summed pain intensity differences and total pain relief. Meaningful pain relief was achieved within a median of 42.3 and 42.9 min for aspirin and paracetamol, respectively, in the dental pain model. The corresponding numbers in sore throat pain were 48.0 and 40.4 min. All treatments in both studies were safe and well tolerated. No serious adverse events were reported and no subject was discontinued due to an adverse event. Overall the two studies clearly demonstrated efficacy over placebo in the two pain models and a comparable efficacy and safety profile between aspirin and an equivalent dose of paracetamol under the conditions of acute dental pain and acute sore throat pain. Trial registration These trials were registered with ClinicalTrials.gov, registration number: NCT01420094, registration date: July 27, 2011 and registration number: NCT01453400, registration date: October 13, 2011.     

An evaluation of different doses of soluble aspirin and aspirin tablets in postoperative dental pain.

1. The efficacy of three different single doses (600, 900 and 1200 mg of soluble aspirin and aspirin tablets) was determined in a randomized placebo-controlled parallel study in 140 patients (70 females) with postoperative pain after removal of impacted third molars. 2. Patients treated with soluble aspirin 600 mg, 900 mg, 1200 mg and aspirin tablet 1200 mg reported significantly less pain (P less than 0.01) throughout the investigation period than those treated with placebo. 3. Overall pain scores after treatment with aspirin tablets 600 and 900 mg did not differ significantly from those after treatment with placebo (P greater than 0.05). 4. On a comparative dose basis, soluble aspirin was significantly more potent (P less than 0.05) than aspirin tablets.     

Flurbiprofen in the treatment of primary dysmenorrhoea.

1 In a double-blind crossover study, flurbiprofen produced marked relief of pain which was significantly more than with aspirin and placebo in patients suffering from primary dysmenorrhoea. In contrast, there was no significant difference between the relief of pain obtained with aspirin and placebo. 2 The clinician's overall assessment of efficacy also indicated that flurbiprofen produced better response as compared to aspirin and placebo in these patients with dysmenorrhoea. 3 Both flurbiprofen and aspirin did not produce any apparent adverse effects on blood loss during the menstrual period. 4 In conclusion, the analgesic effect of flurbiprofen seen in this trial establishes the therapeutic usefulness of the drug in the treatment of primary dysmenorrhoea.     

Analgesic effect of naproxen sodium, codeine, a naproxen-codeine combination and aspirin on the postoperative pain of oral surgery

In a double-blind study, 198 outpatients with pain after oral surgery were randomly assigned to treatment with a single oral dose of naproxen sodium 550 mg, codeine sulfate 60 mg, a combination of naproxen sodium 550 mg with codeine sulfate 60 mg, aspirin 650 mg or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 12 hours after medication. Orthogonal contrasts for the four treatments making up the factorial component showed that the naproxen effect was significant for every measurement of total and peak analgesia; the codeine effect was significant for total and peak pain relief and patients' overall evaluation. The naproxen-codeine interaction was not statistically significant for any measure, which suggests that the analgesic effect of the combination represents the additive effect of its constituents. Based on pairwise comparisons, aspirin was significantly superior to placebo for most measures of effect, naproxen was significantly superior to both aspirin and codeine for all measures and the combination was significantly superior to naproxen for patients' overall evaluation. No more patients experienced adverse effects with aspirin or naproxen than with placebo, but significantly more patients receiving the codeine-containing treatments experienced adverse effects than those receiving aspirin and naproxen.     

Ketorolac versus aspirin for postpartum uterine pain

Ketorolac tromethamine, a new nonsteroidal antiinflammatory analgesic, was evaluated for relative efficacy, safety and time course of analgesia in a stratified, randomized, parallel, double-blind trial. The study involved 120 hospitalized women (4 groups of 30) with moderate or severe postpartum uterine pain treated with single oral doses of ketorolac 5 mg and 10 mg, aspirin 650 mg or placebo. At regular interviews for 6 hours patients rated pain intensity, pain relief and side effects. Significant differences (p less than or equal to 0.05, two-tailed) occurred among the 4 treatments for various measurements of summed and peak analgesia. Ketorolac 10 mg was significantly superior to placebo in 5 of 5 major efficacy measurements, and aspirin was significantly superior in 3 of 5. Ketorolac 10 mg gave the highest mean rating for summed pain intensity differences (13.6, p = 0.0002 versus placebo), followed by aspirin (11.9, p = 0.012), ketorolac 5 mg (10.9, p = 0.072) and placebo (8.6). With ketorolac 10 mg and 5 mg and aspirin, analgesia lasted 6 hours, with peak efficacy at 3 hours. Side effects were not significant. Our results suggested a positive dose-response relationship for ketorolac. Compared to aspirin, ketorolac 10 mg induced equal or more analgesia, whereas ketorolac 5 mg was near the minimum effective dose and seemed less effective than aspirin.     

Oral ciramadol: a new analgesic for postoperative pain

Ciramadol, a new synthetic narcotic agonist-antagonist analgesic, was compared in 30 and 60 mg doses with pentazocine 50 mg, aspirin 650 mg, and placebo in the treatment of 153 patients with postoperative pain. All drugs were administered between six and 72 hours after surgery. Analgesic efficacy was assessed for six hours after study drug administration using verbal pain intensity, analog pain intensity, and verbal pain relief scales. Significantly (P less than .05) higher analgesic efficacy scores were seen with ciramadol 30 mg than with pentazocine 50 mg and placebo at most of the evaluation points. Doses of ciramadol 30 mg were significantly (P less than .05) more effective than aspirin 650 mg at several time periods, and ciramadol 60 mg was better than pentazocine and placebo at several evaluation times. The 30-mg dose of ciramadol was generally more effective than the 60-mg dose. The mean six-hour cumulative sum of pain intensity difference scores, total pain relief scores, and sum of pain analog intensity difference scores showed that the best analgesic response occurred in the ciramadol 30 mg group, followed by the ciramadol 60 mg, aspirin 650 mg, pentazocine 50 mg, and placebo groups. Side effects were rare and mild. There were no medically important changes in vital signs in any treatment group.     

A comparative oral analgesic study of indoprofen, aspirin, and placebo in postpartum pain

The purpose of this study was to evaluate the analgesic efficacy and adverse effect liability of single oral doses of indoprofen, 50 mg, 100 mg, and 200 mg, compared with aspirin, 300 mg and 600 mg, and placebo in the relief of moderate to severe postpartum pain. Two hundred-ten patients entered a randomized, double-blind, parallel group study and were evaluated over a six-hour period by a single nurse-observer. There was a significant imbalance in the distribution of pain types across treatments that compromises the interpretation of the results. In addition to analyzing the data from all patients, the subsets with episiotomy/cesarean section pain and uterine cramp pain were examined separately. The latter group had too few patients to permit distinction between drugs. The 100 mg and 200 mg doses of indoprofen were significantly (P less than or equal to .05) more effective than placebo for many variables including the following summary values: sum of pain intensity difference (SPID), sum of hourly relief values (TOTPAR), and % SPID for all patients as well as in the subset of patients with episiotomy/cesarean section pain. Aspirin, 600 mg, was also significantly more effective than placebo for many of the same measures of analgesia in the episiotomy/cesarean section subset. Pairwise differences were also seen between placebo and aspirin, 300 mg, but on fewer variables. Indoprofen, 100 mg, was significantly more effective than aspirin, 600 mg, at hour 6 for pain intensity difference (PID) in the episiotomy/cesarean section subset. The effect of indoprofen appeared to plateau above 100 mg.(ABSTRACT TRUNCATED AT 250 WORDS)     

A double-blind comparison of diflunisal and aspirin in the treatment of post-operative pain after episiotomy.

A double-blind randomized trial was carried out in 161 primiparous women suffering from moderate to severe post-episiotomy pain to compare the analgesic efficacy of single doses of diflunisal (125 mg, 250 mg, of 500 mg), aspirin (600 mg), and placebo. The results of pain rating assessments made before and at hourly intervals after drug administration showed that both the active drugs were more effective than placebo and produced similar pain relief over the first 4 hours. The analgesic efficacy of aspirin tailed off after 4 hours but pain relief with 500 mg diflunisal was still evident after 8 hours. Over 65% of patients in the diflunisal group had effective relief of pain at 8 hours whereas there was no significant difference between the aspirin and placebo-treated groups by the seventh and eighth hour.     

Evaluation of the therapeutic potential of ketoprofen in rheumatoid arthritis

Summary

A single-blind, non-crossover trial of ketoprofen in 2 dose schedules, compared with ibuprofen, has been carried out in 135 patients with rheumatoid arthritis. The results are also compared with those obtained for prednisone, aspirin, indomethacin and paracetamol in 2 previous studies using the same method.

The trial method employed showed ketoprofen to be significantly more effective than placebo in terms of patient satisfaction rating, but less effective than prednisone. In terms of pain relief, ketoprofen appeared to be more effective than placebo, although the differences did not reach significant levels. The trial, however failed to demonstrate significant differences either between ketoprofen, ibuprofen, aspirin, indomethacin and paracetamol, or between ketoprofen at 2 widely separate dose levels.     

A double-blind comparison of diflunisal and aspirin in the treatment of post-operative pain after episiotomy

Summary

A double-blind randomized trial was carried out in 161 primiparous women suffering from moderate to severe post-episiotomy pain to compare the analgesic efficacy of single doses of diflunisal (125?mg, 250?mg, or 500?mg), aspirin (600?mg), and placebo. The results of pain rating assessments made before and at hourly intervals after drug administration showed that both the active drugs were more effective than placebo and produced similar pain relief over the first 4 hours. The analgesic efficacy of aspirin tailed off after 4 hours but pain relief with 500?mg diflunisal was still evident after 8 hours. Over 65% of patients in the diflunisal group had effective relief of pain at 8 hours whereas there was no significant difference between the aspirin and placebo-treated groups by the seventh and eighth hour.     

Comparison of etodolac, aspirin and placebo for pain after oral surgery

Single oral doses of etodolac 50, 100 and 200 mg were compared with aspirin 650 mg and placebo in a double-blind, parallel group study of 189 outpatients reporting moderate or severe pain after oral surgery. Overall efficacy of test drugs was evaluated by sum of pain intensity difference (SPID) scores and total pain relief (TOTPAR) scores over 0.5-3, 0.5-6, 0.5-8 and 0.5-12 hours. Etodolac 200 mg provided significantly greater analgesia than aspirin by these measurements over all SPID and all but one TOTPAR interval, and was significantly more effective than placebo over all intervals. Etodolac 100 mg was superior to aspirin for SPID 0.5-8 and 0.5-12 hours, and superior to placebo for both SPID and TOTPAR over all time intervals. Onset of analgesia for etodolac 100 mg, 200 mg and aspirin was 1 hour or less for the majority of patients in each group; 42% receiving etodolac 200 mg reported onset of analgesia within 0.5 hour. Duration of analgesia for etodolac 200 mg appeared twice that of aspirin. A significant positive dose-response relationship was obtained for the three doses of etodolac. A low frequency of side effects was observed in all treatment groups.     

The effect of itazigrel and aspirin on the mucosa of the esophagus, stomach, and duodenum of normal subjects

The effects of aspirin, itazigrel (U-53,059; a new antiplatelet drug), and placebo on the mucosa of the esophagus, stomach, and duodenum were evaluated in this double-blind, randomized, placebo-controlled study. Six normal male subjects were included in each of five treatment groups: aspirin (325 mg each morning for five doses), aspirin (325 mg tid for 12 doses), itazigrel (25 mg each morning for five doses), itazigrel (50 mg tid for 12 doses), and placebo. Aspirin and itazigrel, at all doses investigated, significantly inhibited ex vivo, ionophore (A23187)-stimulated thromboxane B2 synthesis. Collagen-induced platelet aggregation was significantly inhibited on day 3 (P = .021) and day 5 (P = .002) in both aspirin and itazigrel groups as compared with placebo. Upper gastrointestinal endoscopy was performed before the first dose of drug (day 1) and two hours after the last dose (day 5) for each subject. A rating scale was used to score the amount of mucosal damage. The baseline (day 1) endoscopic scores revealed no significant differences between groups. On day 5, neither placebo nor itazigrel treatment groups showed any significant change compared with baseline. On day 5, both aspirin groups had significantly (P less than .001) more mucosal damage than the placebo group and either itazigrel group. It is concluded that in this relatively acute study, at doses that produce comparable inhibition of platelet aggregation and platelet cyclo-oxygenase, itazigrel was superior to aspirin in terms of toxicity to the upper gastrointestinal tract.     

Analgesic effect of fendosal, ibuprofen and aspirin in postoperative oral surgery pain

The analgesic efficacy of a single 200-mg dose of fendosal, a nonnarcotic, nonsteroidal antiinflammatory analgesic, was compared, in a double-blind study, with aspirin 650 mg, ibuprofen 400 mg and placebo in outpatients who had moderate or severe pain after the surgical removal of impacted third molars. Using a self-rating record, patients rated their pain and its relief hourly for up to 12 hours after medicating. Each active medication was significantly superior to placebo. The peak analgesic effect of fendosal 200 mg was similar to that of the aspirin 650-mg standard. Although fendosal's onset of action was slow (3 hours), its effect persisted for 8 hours, substantially longer than that of aspirin. Ibuprofen 400 mg was statistically significantly superior to aspirin 650 mg and fendosal 200 mg for most measures of peak and total analgesia, and its effect persisted for 8 hours. The results of this study raise some questions concerning the comparability of data from studies that employ different criteria for remedication and/or different criteria for the inclusion of data in the analyses of efficacy.     

Aspirin metabolism and efficacy in postoperative dental pain

Aspirin 1200 mg was compared with placebo in a randomised, double-blind, crossover study in 15 patients with postoperative pain after removal of impacted lower third molars. Over a 5 h investigation period, patients reported significantly less pain (P less than 0.01) after treatment with aspirin, than after treatment with placebo. Peak concentrations of aspirin occurred at 15 min after dosage. Significant negative correlations were observed between plasma aspirin esterase activity and both AUC aspirin (r = -0.904, P less than 0.001) and AUC analgesia (r = -0.91, P less than 0.001). Similarly, a significant correlation was observed between AUC aspirin and AUC analgesia (r = 0.96, P less than 0.001). Evidence from this study would suggest that an individual's pain relief in postoperative dental pain is determined by the rate of aspirin hydrolysis to salicylate.     

The onset of action and the analgesic efficacy of Saridon (a propyphenazone/paracetamol/ caffeine combination) in comparison with paracetamol, ibuprofen, aspirin and placebo (pooled statistical analysis)

The objective was to evaluate the onset of action, analgesic efficacy and tolerability of Saridon*, a propyphenazone 150 mg/paracetamol 250 mg/caffeine 50 mg combination, in comparison with paracetamol 500 mg, aspirin 500 mg, ibuprofen 200 mg and placebo, by a pooled statistical analysis of eight studies. Out of 500 generally healthy patients (55.2% men, 44.8% women), average age 43.5 years, 329 (65.8%) had moderate and 171 (34.2%) severe acute dentoalveolar pain. More Saridon-treated patients reported 'pain gone/partly gone' and less 'pain unchanged or worse' compared with paracetamol, aspirin and placebo 30min (p = 0.009, p < 0.001, p = 0.001, respectively) and 60 min after dosing (p < 0.0001 for all). The difference with ibuprofen was observed 60 min after dosing (p < 0.01). Pain intensity differences 30 min and 60 min after dosing infer that Saridon has a faster onset of action than all of the other medications that it was compared with (ibuprofen at only 60 min after dosing). Total pain relief scores four hours after dosing were higher in the Saridon group compared with the paracetamol, ibuprofen, placebo (p < 0.0001 for all) and aspirin groups (p < 0.01). At the end of the study, patients assessed Saridon as more efficacious than the other study medications (p < 0.0001 for all). No serious adverse events were observed with any of the drugs studied. All medications were well tolerated. Twenty patients (4.0%) reported adverse events with no significant differences between groups. The most common adverse events were gastrointestinal disorders, followed by nervous system, skin, subcutaneous tissue, respiratory, cardiac and general disorders. Saridon is an effective analgesic that combines the advantage of fast onset and effective analgesia as compared with paracetamol alone, ibuprofen, aspirin or placebo. The results of this pooled analysis of eight studies should be confirmed in a double-blind study, since seven of the studies included in this analysis were single blind.     

Analgesic efficacy of amfenac, aspirin and placebo after extraction of impacted teeth

Amfenac, an arylacetic acid derivative, is a new investigational, nonsteroidal antiinflammatory agent that has exhibited analgesic properties superior to those of phenylbutazone in animals. This double-blind, randomized, parallel study was an early clinical trial to evaluate the analgesic efficacy of one oral dose of amfenac 100 mg compared to aspirin 600 mg and placebo in 120 subjects with moderate to severe pain after extraction of impacted molar teeth. Self-evaluated subjective pain intensity and relief reports for 4 hours were used as indexes of response. Analgesic effects of amfenac were significantly superior to those of placebo (p less than 0.001) and aspirin (p less than 0.05) by most measurements. Aspirin 600 mg was superior to placebo based on total pain relief and global scores (p less than 0.05). Compared with aspirin 600 mg, amfenac 100 mg provided greater and faster analgesia, lasting at least for 4 hours. Ordinal pain intensity scores correlated well with the visual pain analog scale. Seven (17.5%) patients taking amfenac compared to 5 (12.5%) taking placebo reported minor adverse effects).     

Comparative efficacy of soluble aspirin and aspirin tablets in postoperative dental pain

Summary The efficacy of single doses (1.2 g) of soluble aspirin and aspirin tablets was determined in a randomised, placebo-controlled, double-blind, parallel study in 90 patients (45 females) with postoperative pain after removal of impacted lower third molars. Also investigated was the relationship between plasma aspirin esterase activity and overall pain scores after both aspirin preparations. Patients reported significantly less pain (p<0.001) after treatment with aspirin than after treatment with placebo. However, patients receiving soluble aspirin reported both an earlier onset and a longer duration of pain relief than those who received aspirin tablets. A significant correlation was observed between plasma aspirin esterase activity and overall pain scores after both soluble aspirin (r=0.57,p<0.01) and aspirin tablets (r=0.51,p<0.02). It is concluded that soluble aspirin is the preferred aspirin formulation for treating postoperative pain after third molar surgery and that plasma aspirin esterase activity is a determinant of a patient's analgesic response to aspirin in postoperative dental pain.     

Etodolac. A preliminary review of its pharmacodynamic activity and therapeutic use

Etodolac is a new non-steroidal agent (NSAID) with anti-inflammatory and analgesic activity. It has been studied in rheumatoid arthritis, osteoarthritis, and pain resulting from minor surgery. In the latter setting, etodolac is at least as effective as aspirin in terms of overall pain relief, and the duration of analgesic effect of a dose of 200 to 400mg is longer than that of aspirin. In rheumatoid arthritis, etodolac, administered twice daily, appears comparable in efficacy to moderate doses of aspirin (3 to 4g daily), but is better tolerated. To date, etodolac has not been compared clinically with analgesics other than aspirin and sulindac. As with other non-steroidal agents, gastrointestinal complaints are the most frequently reported side effects, but the incidence of most gastrointestinal effects was only slightly higher than with placebo. Thus, from studies in small numbers of patients etodolac appears at least as effective as aspirin and better tolerated. The relatively low incidence of gastrointestinal side effects in these studies awaits confirmation in well designed comparisons with widely used NSAIDs.     

Analgesic effect of graded doses of flurbiprofen in post-episiotomy pain

Our purpose was to evaluate the analgesic efficacy and safety of single oral doses of flurbiprofen 25, 50 and 100 mg, aspirin 600 mg, and placebo in the relief of moderate to severe post-episiotomy pain. One hundred and fifty-two evaluable patients completed a randomized, double-blind, stratified, parallel groups study. They were observed over a six hour period by one nurse-observer. Based upon each of the summary efficacy measures SPID, TOTAL and PEAK % and most of the hourly direct measures of pain intensity and pain relief, each of the four active treatments were statistically superior to placebo. Flurbiprofen 25 mg appeared to be slightly less effective than aspirin 600 mg, but the differences were not statistically significant. Flurbiprofen 50 and 100 mg were quite similar and were significantly more effective than aspirin 600 mg and flurbiprofen 25 mg. There were no observed or reported adverse effects.