The relative analgesic potency of oxymorphone by rectal suppository and intramuscular injection was evaluated in a double-blind, twin-crossover comparison of graded single doses in 136 patients with postoperative pain. The time-effect curves of the two routes of administration differed substantially; rectal resulted in lower and more delayed peak analgesia and a longer duration of action than intramuscular administration. When both duration and intensity of analgesia are considered (total effect), rectal oxymorphone was 1/10 as potent as the intramuscular form; in peak effect, it was only 1/16 to 1/20 as potent. However, because intramuscular oxymorphone is nine to ten times as potent as intramuscular morphine, 5 to 10 mg oxymorphone by suppository provides analgesia comparable to that provided by the usually used doses of parenteral narcotics. Rectal oxymorphone produced no more, and perhaps somewhat fewer, side effects than doses of intramuscular oxymorphone producing equivalent total analgesic effect. None of the patients objected to the rectal route of analgesic administration. This study demonstrates the feasibility of well-controlled analgesic assays employing the double-dummy technique to compare suppositoreis with oral or parenteral analgesic dosage forms. Our observations also suggest that the rectal route is an acceptable and practical way of administering potent analgesics and is probably being underutilized by physicians in the control of moderate to severe pain.

Adult↗

PubMedDate not supplied

Twin crossover relative potency analgesic assays in man. I. Morphine vs. morphine.

Although the four-point relative potency assay using crossover design has proven a powerful technique for the clinical evaluation of analgesics in patients with chronic pain, excessive dropouts have made this design impractical in postoperative pain. In a relative potency assay comparing single graded intramuscular doses of morphine standard and morphine test in postoperative patients, we have managed to circumvent this difficulty while preserving many of the advantages of a complete crossover by using the "twin-crossover" balanced incomplete block design, which requires that each subject receive only two of the four possible treatments. The "twin crossover" design, coupled with a sequential decision-making process that expedites choosing the doses of the test medication which are most closely equianalgesic with the standard, yielded excellent analgesic assay sensitivity and made efficient use of our population of postoperative patients.

Adult↗

PubMedDate not supplied

Twin crossover relative potency analgesic assays in man. II. Morphine vs. 8-methoxycyclazocine.

Using the twin crossover, balanced incomplete block design described in the previous paper, a double-blind determination of the relative analgesic potency of graded intramuscular doses of Win 20,836 (8-methoxycyclazocine) and morphine was carried out in patients with postoperative pain. Although no preliminary data at all on the human analgesic activity of Win 20,836 were available, the sequential decision-making process designed to choose the doses of the test medication most closely equianalgesic with the standard functioned efficiently to establish doses of Win 20,836 that had analgesic activity. Unfortunately, the occurrence of psychotomimetic side effects prevented the administration of doses of Win 20,836 equieffective with the morphine standard, and this necessitated substantal extrapolation of the dose-response curve of the test drug to arrive at a relative potency estimate. However, our relative potency estimate, which indicated that Win 20,836 is three to six times as potent as morphine, was dependable enough to predict with reasonable certainty that doses of Win 20,836 equieffective to the usual doses of morphine would produce an unacceptable level of psychotomimetic side effects. Clinical investigation of the drug was therefore terminated.

Analgesics, Opioid↗

PubMedDate not supplied

A 12-hour evaluation of the analgesic efficacy of diflunisal, aspirin, and placebo in postoperative dental pain.

Two-hundred and one outpatients with postoperative pain following oral surgery were randomly assigned, on a double-blind basis, a single oral dose of diflunisal (250, 500, or 1000 mg), aspirin (650 mg), or placebo. Using a self-rating record, the subjects rated their pain and its relief hourly for 12 hours after medication. Measures of peak and total analgesia were derived from the patients' subjective reports. Diflunisal 250 and 1000 mg were significantly superior to aspirin for every measure of total and peak analgesia; the 500-mg diflunisal dose was significantly superior to aspirin for measures of total analgesia only. All doses of diflunisal were significantly superior to aspirin and placebo at each hour from hour 3 through hour 12. Approximately 60 per cent of the patients treated with diflunisal completed the 12-hour observation period without the need for additional analgesic therapy. Adverse effects were mild and transitory and occurred in less than 10 per cent of the patients.

Adult↗

PubMedDate not supplied

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.

Adolescent↗

PubMedDate not supplied

A 12-hour evaluation of the analgesic efficacy of diflunisal, zomepirac sodium, aspirin, and placebo in postoperative oral surgery pain.

One hundred ninety-nine outpatients with pain following oral surgery were randomly assigned, on a double-blind basis, a single oral dose of diflunisal (500 or 1,000 mg), zomepirac sodium 100 mg, aspirin 650 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 12 hours after medication. Measures of total and peak analgesia were derived from these patients' subjective reports. Diflunisal (500 and 1,000 mg) and zomepirac were significantly superior to aspirin and placebo for every measure of total and peak analgesia. Based upon the first 4 hours of observation, aspirin was superior to placebo for every measure of analgesia. Diflunisal 500 and 1,000 mg were comparable to zomepirac in peak analgesia and significantly superior to zomepirac for all measures of total analgesia. The onset of analgesia was comparable for 1,000 mg diflunisal, zomepirac, and aspirin, but more rapid for these treatments than for 500 mg diflunisal. The duration of analgesia was 12 hours for diflunisal, 9 hours for zomepirac, and 3 hours for aspirin.

Analgesics↗

PubMedDate not supplied

A 12-hour evaluation of the analgesic efficacy of diflunisal, acetaminophen, and acetaminophen-codeine combination, and placebo in postoperative pain.

The analgesic efficacy of single 500 and 1,000 mg doses of diflunisal, a new nonsteroidal antiinflammatory analgesic, was compared in a double-blind study with acetaminophen 600 mg, the combination of acetaminophen 600 mg with codeine 60 mg, and placebo in 132 inpatients with postoperative pain. Using a self-rating record, patients rated their pain and its relief hourly for up to 12 hours after medication. Diflunisal 500 and 1,000 mg were significantly superior to placebo for every measure of total and peak analgesia, and a significant analgesic effect persisted for 8 hours. Acetaminophen alone and the acetaminophen-codeine combination were significantly superior to placebo for most measures of analgesia, and their effects were significant for 4 and 5 hours respectively. Differences among the active medications were not statistically significant for measures of total or peak analgesia.

Acetaminophen↗

PubMedDate not supplied

A method for the 12-hour evaluation of analgesic efficacy in outpatients with postoperative oral surgery pain. Three studies of diflunisal.

We have developed a method for measuring the efficacy of a single dose of an analgesic for 12 hours after administration of outpatients with postoperative oral surgery pain. Using a self-rating record, patients evaluate their pain and its relief for 12 hours after medication. We have used this method successfully in a series of three studies to compare diflunisal, a new nonsteroidal antiinflammatory analgesic, with placebo and aspirin 650 mg, acetaminophen 600 mg, propoxyphene napsylate 100 mg, or a combination of acetaminophen with either codeine 60 mg or propoxyphene 100 mg. Diflunisal evinced an unusually long duration of analgesic effect. In each study, all doses of diflunisal were significantly superior to placebo through the end of the 12-hour observation period, while the standards were superior for periods ranging from 2 to 7 hours. In terms of peak analgesia, diflunisal 1,000 mg was comparable to the acetaminophen-codeine combination and was significantly superior to all the other analgesic standards.

Acetaminophen↗

PubMedDate not supplied

Zomepirac: an overview--concluding remarks of the symposium chairman.

Explore the source record for details and available documents.

Analgesics↗

PubMedDate not supplied

Evaluation of bromfenac and ibuprofen for pain after orthopedic surgery.

STUDY OBJECTIVES: To determine the relative analgesic potency and adverse effect liability of bromfenac 25, 50, and 100 mg, and ibuprofen 200 and 400 mg in the treatment of postoperative pain after orthopedic surgery. DESIGN: Randomized, double-blind, single-dose, parallel-group relative potency assay with evaluations at 30 minutes and then at hourly intervals for up to 6 hours. SETTING: Two wards of the orthopedic surgery department at the Centralsjukhuset (Central Hospital) in Karlstad, Sweden. PATIENTS: Two hundred inpatients with steady, moderate or severe pain within 72 hours after orthopedic surgery. INTERVENTIONS: Patients received a single oral dose of bromfenac 25, 50, or 100 mg, or ibuprofen 200 or 400 mg, when they experienced steady, moderate or severe pain that, in their opinion, required an analgesic. Using a self-rating record, subjects rated their pain and its relief for 6 hours after medicating. MEASUREMENTS AND MAIN RESULTS: The study was a valid relative potency assay with estimates of bromfenac's potency relative to ibuprofen ranging from 10.9 (nurse's global evaluation) to 16.7 (sum of hourly analog pain intensity difference scores). That is, 11-16 times the dose of ibuprofen must be administered to equal the analgesic effect of bromfenac. Patients who had eaten breakfast or lunch within 60 minutes before or 30 minutes after receiving the study medication ("fed" patients) had lower efficacy scores than those who had not ingested food within these time constraints before or after receiving the study medication ("fasted" patients). Furthermore, patients who had eaten before receiving the study medication had significantly lower efficacy scores than those who had eaten after receiving the study medication. CONCLUSIONS: The relative potency of the analgesic effect of bromfenac to ibuprofen is 11-16.7 in patients with pain after orthopedic surgery. Fed patients may have lower analgesic efficacy than fasted patients. Adverse effects for both bromfenac and ibuprofen were transient and consistent with the pharmacologic profiles of the drugs.

Analgesics↗