Abraham Sunshine

The correlation between blood levels of ibuprofen and clinical analgesic response

A clinical trial comparing ibuprofen, 400, 600, and 800 mg, with aluminum ibuprofen, 400 mg, and placebo was conducted in patients with moderate or severe pain subsequent to third molar extraction. Pain intensity ratings and ibuprofen serum levels were obtained at baseline, 30 minutes, 1 hour, and hourly thereafter for 3 hours. Pain intensity ratings were also obtained at hours 4, 5, and 6. Serum levels at 1, 2, and 3 hours correlated significantly with the log dose of ibuprofen (r = 0.35, 0.49, and 0.48, respectively) and with global analgesic response as measured by the percentage of the sum of the pain intensity scores (r = 0.28, 0.34, and 0.26, respectively). However, possibly because of differences in drug formulation, the percentage of the sum of the pain intensity scores did not correlate significantly with log dose. The highest correlations were found between contemporaneous serum levels and pain intensity difference values, particularly at hour 1 (r = 0.54). Our results support the proposition that increased ibuprofen serum levels lead to increased analgesia.

Effect of caffeine on acetaminophen analgesia

Our objective was to determine the value of caffeine in combination with acetaminophen in the relief of pain from uterine cramping, episiotomy, and third molar extraction. In the dental study, 173 patients received two or four tablets of 500 mg acetaminophen or the combination of 500 mg acetaminophen and 65 mg caffeine. In the three postpartum studies, 1345 patients received one, two, or three tablets of acetaminophen, the combination, or a placebo. The mean scores for the summary variable percent sum of the pain intensity differences (% SPID) were higher in all for the combination than for acetaminophen alone, and in two studies the null hypothesis of no differences was rejected. The relative potency estimates for % SPID were 1.9, 1.8, and 1.3 for the three studies in which bioassays could be performed and the pooled relative potency was 1.7 with a 95% confidence interval of 1.1 to 3.1. The results were essentially the same among pain models and among patient groups with similar habitual caffeine consumption. Onset of analgesia was also faster with the combination. We conclude that caffeine enhances the analgesic efficacy of acetaminophen.

Herpes zoster encephalitis.

Abstract This report summarizes the experience with fourteen cases of herpes zoster encephalitis. The pathology is discussed on the basis of reports in the literature. It has been noted that the pathologic changes usually are in the nature of a disseminated encephalomyelitis, with lymphocytic infiltration and partial demyelination. The clinical manifestations are described. In the majority of the cases the clinical picture reflected an acute meningoencephalitic insult, with fever, change in the sensorium and signs of meningeal irritation. The clinical course was usually short, with recovery in one to three weeks. The spinal fluid was usually clear, with an increase in cells, predominantly lymphocytes. An increase in the protein content was noted in slightly more than half the cases. The sugar content was generally normal and cultures were sterile. Weak first zone colloidal gold curves were obtained in two of the cases. Electroencephaograms were obtained in three cases, in two of which the tracings were abnormal. No deaths occurred in this series during the acute phase of the disease. In a follow-up study of nine patients, six escaped without neurologic residua and three showed sequelae. In two of the latter patients abnormal electroencephalograms and abnormal colloidal gold curves were obtained early in the disease. Of special interest was the occurrence of a varicelliform eruption in four patients. The relationship between herpes zoster and varicella is discussed. Treatment was in the main symptomatic. The use of hormonal therapy merits further investigation.

Analgesic oral efficacy of tramadol hydrochloride in postoperative pain.

Tramadol hydrochloride is a synthetic opiate agonist with a plasma elimination half‐life of 5 to 6 hours and peak plasma levels at about 1½ hours. It derives its activity from attachment to the μ‐receptor and blockage of norepinephrine reuptake. The purpose of this single‐dose, double‐blind, placebo‐controlled study was to determine the analgesic effectiveness of an oral administration of two dose levels of tramadol hydrochloride (75 or 150 mg) compared with the combination of 650 mg acetaminophen plus 100 mg propoxyphene napsylate in 161 patients with severe postoperative pain after cesarean section. Analgesia was assessed over a 6‐hour period. Treatments were compared on the basis of standard scales for pain intensity and relief and a number of derived variables based on these data. A global rating of the study medication was also used to compare treatments. The three active treatments were effective analgesics, statistically superior to placebo for many hourly and summary measures. A dose response was seen between the two tramadol doses, with the 150 mg dose providing significantly greater analgesia over the lower dose. The 75 mg dose of tramadol was generally more effective than the acetaminophen‐propoxyphene combination after hour 2, and significantly so for some hourly time points, as well as for the global rating of the medication. The 150 mg dose of tramadol was significantly more effective than the acetaminophen‐propoxyphene combination from hour 2 through hour 6 for the sum of pain intensity differences and total pain relief scores, as well as for the global rating of the medication. Tramadol hydrochloride at both dose levels is an effective analgesic agent and at 150 mg is statistically superior to the acetaminophen‐propoxyphene combination. No serious adverse effects were observed; however, dizziness was more frequently reported with 150 mg tramadol.

Analgesic efficacy of controlled-release oxycodone in postoperative pain.

The efficacy and safety of graded doses (10, 20, and 30 mg) of controlled‐release (CR) oxycodone was compared with that of immediate‐release (IR) oxycodone (15 mg), immediate‐release oxycodone 10 mg in combination with acetaminophen 650 mg (APAP), and placebo in a single‐dose, double‐blind, randomized, parallel‐group study. The participants, 182 inpatients experiencing moderate to severe pain after abdominal or gynecologic surgery, provided hourly ratings of pain intensity and relief for 12 hours after administration. All active treatments were significantly superior to placebo for many hourly measurements and for the sum of pain intensity differences (SPID) and total pain relief (TOTPAR). A dose response was found among the three levels of CR oxycodone for pain relief and peak pain intensity difference (PID), with the 20‐ and 30‐mg doses being significantly better than the 10‐mg dose. For all active treatments, peak PID and peak pain relief occurred approximately 2 to 4 hours after administration. The median time to onset of relief was 32 minutes for oxycodone plus APAP, 41 minutes for IR oxycodone, and 46 minutes for CR oxycodone 30 mg. Duration of pain relief showed that the 10‐, 20‐, and 30‐mg doses of CR oxycodone had durations of action of 10 to 12 hours compared with IR oxycodone and oxycodone plus APAP (both approximately 7 hours). Typical adverse events, particularly somnolence, occurred in all active treatment groups. Treatment with CR oxycodone was safe and effective in this study, and its characteristics will be beneficial in the treatment of pain.

Nefopam and morphine in man.

A new analgesic, nefopam, is chemically distinct and pharmacologically unrelated to any presently known analgesic. A comparison was made of morphine and nefopam in 74 patients who required parenteral analgesia for moderate to severe postoperative and somatic pain, using a single administration, 2‐dose level, double‐blind design. A significant dose‐response curve was obtained with nefopam and with morphine, and there was no significant deviation from parallelism. The time‐effect curves for the 2 drugs were similar. The estimated relative potency of nefopam to morphine indicates that 20 mg of neJopam HCI is the approximate analgesic equal of 12 mg of morphine SO4. There were no adverse effects with nefopam and one adverse reaction to morphine.

Analgesic Efficacy of a Hydrocodone with Ibuprofen Combination Compared with Ibuprofen Alone for the Treatment of Acute Postoperative Pain

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. J Clin Pharmacol 1997;37:908–915.

ONSET AND DURATION : MEASUREMENT AND ANALYSIS

Clinical Pharmacology and Therapeutics (1991) 49, 1–5; doi:10.1038/clpt.1991.1

Analgesic Efficacy of Ketoprofen in Postpartum, General Surgery, and Chronic Cancer Pain

This article summarizes the results of five single‐dose clinical studies of three pain models: postpartum, postoperative, and chronic cancer pain. The efficacy of ketoprofen (in varying doses from 25 to 225 mg) was compared with one of the following standards: aspirin (650 mg), codeine (90 mg), acetaminophen (650 mg) plus codeine (60 mg), and parenteral morphine (5 mg and 10 mg). The results indicate that ketoprofen in doses as low as 25 mg has analgesic properties significantly superior to those of placebo. For the treatment of postpartum pain, ketoprofen was significantly more effective than aspirin 650 mg but not significantly different from codeine 90 mg. Ketoprofen doses of 50 mg and 150 mg also provided analgesia superior to that with acetaminophen 650 mg plus codeine 60 mg for the management of moderate to severe postoperative pain. Moreover, oral doses of ketoprofen (75 and 225 mgj provided analgesia similar to that obtained with 5 and 10 mg parenteral doses of morphine. Adverse effects related to ketoprofen were relatively minor and infrequent. Ketoprofen was recently approved for use as an analgesic for treatment of mild to moderate pain in total daily doses up to 300 mg; the recommended initial dose is 25 to 50 mg every 6 to 8 hours as necessary.

Analgesic efficacy of two ibuprofen‐codeine combinations for the treatment of postepisiotomy and postoperative pain

Our purpose was to compare the analgesic efficacy and safety of single oral doses of the combination of ibuprofen 400 mg plus codeine 60 mg and the combination of ibuprofen 200 mg plus codeine 30 mg with ibuprofen 400 mg alone, codeine sulfate 60 mg alone, and placebo. One hundred ninety‐five patients with severe pain resulting from episiotomy, cesarean section, or gynecologic surgery completed a randomized, double‐blind, stratified, parallel‐group study. Patients were observed during a 4‐hour period after medication. Based on the sum of the pain intensity differences (SPID), total pain relief (TOTPAR), and most of the hourly direct measures of pain and relief, both doses of the combination and ibuprofen 400 mg alone were statistically superior to placebo. Codeine 60 mg was statistically superior to placebo based on TOTPAR, the global ratings, and a few hourly measures. The mean effect of the combination of ibuprofen 400 mg plus codeine 60 mg was significantly superior to the mean effect of ibuprofen 400 mg alone ½, 1, and 2 hours after medication and to the mean effect of ibuprofen 400 mg alone and codeine 60 mg alone for SPID, TOTPAR, and other measures as well. The low‐dose combination was significantly more effective than codeine 60 mg for a few hourly measures but was not significantly superior to ibuprofen 400 mg. Based on these findings it appears that the combination of ibuprofen 400 mg plus codeine 60 mg, particularly in the first few hours after medication, is more efficacious than its constituents.