Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Jul 1988
Comparative StudyThe role of alpha-adrenoceptor blockade in the antihypertensive effects of fenoldopam in humans.
Fenoldopam, a dopamine-1 receptor agonist, has been reported to exhibit alpha-adrenoceptor-blocking actions in intact and isolated animal preparations. To determine whether alpha-adrenoceptor blockade contributes to its antihypertensive properties in humans, the effects of fenoldopam on the pressor responses to norepinephrine and angiotensin II were compared in eight normal volunteers. ⋯ Dose ratios for an increase in mean blood pressure of 10 mm Hg were 3.3 +/- 0.9 for norepinephrine and 3.2 +/- 0.6 for angiotensin II (p not significant). Consequently, fenoldopam is not a selective alpha-adrenoceptor antagonist at therapeutic concentrations in humans.
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Clin. Pharmacol. Ther. · Jul 1988
Comparative StudyCumulative dose-response with infusion: a technique to determine neuromuscular blocking potency of atracurium and vecuronium.
The ability of cumulative dose-response techniques to obtain accurate data is most likely limited by redistribution and elimination of the drug during the study period. Therefore the usefulness of these techniques would be improved by replacing the amount of drug lost. This hypothesis was assessed for the intermediate-duration neuromuscular blockers vecuronium and atracurium, and calculations were made based on a pharmacokinetic model with an effect compartment. ⋯ For atracurium the ED90 was 0.175 +/- 0.009 (SD), 0.206 +/- 0.019 (CD), and 0.179 +/- 0.015 mg/kg (CDI). Calculated values corresponded well with measured values. The calculations predicted that the agreement between single- and cumulative-dose techniques would be improved if (1) the dose increment was increased, (2) the elimination half-life was increased above 20 minutes, or (3) an infusion was added.(ABSTRACT TRUNCATED AT 250 WORDS)
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Clin. Pharmacol. Ther. · Jun 1988
Clinical Trial Controlled Clinical TrialAnalgesic effect of picenadol, codeine, and placebo in patients with postoperative pain.
A double-blind, parallel study was conducted to evaluate the analgesic effect and safety of a single 25 mg oral dose of picenadol, a centrally acting analgesic, and to compare it with a 60 mg dose of codeine and a placebo in patients with postoperative pain. Two sites using similar protocols enrolled a total of 178 inpatients with postoperative pain. ⋯ Both picenadol and codeine were significantly more effective than placebo in reducing pain intensity (mean sum of pain intensity difference scores: picenadol 5.21, codeine 5.19, and placebo 2.82) and increasing total relief (mean total pain relief: picenadol 10.21, codeine 11.07, and placebo 6.96). Adverse experience profiles were similar among the three treatment groups.
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Clin. Pharmacol. Ther. · Dec 1987
Randomized Controlled Trial Clinical TrialThe additive analgesic efficacy of acetaminophen, 1000 mg, and codeine, 60 mg, in dental pain.
In a double-blind, randomized, single-dose trial the analgesic contribution of acetaminophen, 1000 mg, and codeine, 60 mg, was determined. The study was a 2 X 2 factorial experiment in which 120 patients suffering from pain as a result of oral surgery rated their pain intensity and pain relief for up to 5 hours after a single dose of one of: 1000 mg acetaminophen, 60 mg codeine, 1000 mg acetaminophen plus 60 mg codeine, or placebo. The factorial analysis showed that both 1000 mg acetaminophen and 60 mg codeine made a statistically significant (P less than 0.05) contribution to the analgesic effectiveness of the combination on all measures of efficacy (sum of pain intensity differences, largest pain intensity difference, total pain relief, largest pain relief, and time to remedication). The incidence of adverse effects did not appear to differ among the treatments, including placebo.
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Clin. Pharmacol. Ther. · Oct 1987
Randomized Controlled Trial Comparative Study Clinical TrialAnalgesic 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. ⋯ 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 1/2, 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.