Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Nov 1994
Randomized Controlled Trial Multicenter Study Clinical TrialCaffeine as an analgesic adjuvant in tension headache.
Six randomized, double-blind, two-period crossover studies, conducted under similar protocols, compared the efficacy of two analgesic combinations containing caffeine with an acetaminophen 1000 mg control and with a placebo in outpatients with episodic tension-type headaches. In four studies, comprising 1900 patients, the caffeine-containing analgesic consisted of a combination of 500 mg acetaminophen, 500 mg aspirin, and 130 mg caffeine (APAP/ASA/CAF). In two studies, comprising 911 patients, the caffeine-containing analgesic consisted of a combination of 1000 mg acetaminophen and 130 mg caffeine (APAP/CAF). ⋯ The significant analgesic adjuvant effect of caffeine was independent of patients' usual caffeine use or their caffeine consumption in the 4 hours before medication. For each treatment, the pooled analgesic responses for the four studies of APAP/ASA/CAF were virtually superimposable on the responses in the two APAP/CAF studies. The combinations produced more stomach discomfort, nervousness, and dizziness than acetaminophen or placebo.
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Clin. Pharmacol. Ther. · Nov 1994
Randomized Controlled Trial Clinical TrialThe pharmacokinetic-pharmacodynamic (Digit Symbol Substitution Test) relationship of flumazenil in a midazolam steady-state model in healthy volunteers.
To characterize the plasma concentration-effect relationship of flumazenil in the presence of a predefined midazolam level, a double-blind, placebo-controlled, randomized two-way crossover study was conducted in nine healthy male subjects. After reaching a criterion level of midazolam-induced depression of the Digit Symbol Substitution Test (DSST), volunteers received a dose of flumazenil (1.0 mg) or placebo over 1 minute, with the infusion of midazolam continued. ⋯ Flumazenil exhibited a rapid onset (the half-life of equilibration between drug concentration in the blood and drug effect was 3.3 minutes) and short duration of action (the flumazenil plasma concentration causing half-maximal effect was 7.4 ng/ml, which was reached about 1 hour after dosing). The results of this study also show the competitive nature of flumazenil as a midazolam antagonist.
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Clin. Pharmacol. Ther. · Oct 1994
Randomized Controlled Trial Clinical TrialFlumazenil antagonizes the central effects of zolpidem, an imidazopyridine hypnotic.
Zolpidem is a new imidazopyridine-hypnotic that selectively binds to the central omega 1-receptor subtype. A double-blind, randomized, three-way, crossover placebo-controlled study was carried out in nine healthy male volunteers to assess the possible antagonism of central nervous system--depressant effects of zolpidem by flumazenil. Subjects received zolpidem (0.21 mg/kg) or placebo, intravenously, followed 17 minutes later by flumazenil (0.04 mg/kg) or placebo. ⋯ Flumazenil rapidly antagonized clinical sedation in the five subjects who were asleep and significantly reversed the performance decrement within 3 minutes, without any escape phenomenon. Flumazenil did not change zolpidem plasma concentrations, confirming the pharmacodynamic nature of the interaction. Flumazenil may thus be a safe and effective antidote in patients with zolpidem overdosage.
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Clin. Pharmacol. Ther. · Apr 1994
Randomized Controlled Trial Comparative Study Clinical TrialA placebo-controlled model to assay the onset of action of nonprescription-strength analgesic drugs.
The definition and detection of the onset of analgesic drug activity represent two of the more complicated methodologic challenges in clinical pharmacology. We addressed these issues by designing an analgesic assay with frequent posttreatment assessments to identify the first time when a subject experienced relief and when a nonprescription-strength analgesic could be distinguished from placebo. To test the feasibility of conducting this assay, 29 subjects with acute sore throat were randomized to receive 200 mg ibuprofen, 400 mg ibuprofen, or placebo under double-blind conditions. ⋯ Subjects completed each series of assessments efficiently, most within 5 seconds. Each active agent was differentiated from placebo early after treatment (p < or = 0.05), and there was dose-separation. We conclude that the sore throat pain model can be used to evaluate the onset of action of nonprescription-strength analgesic agents.
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Clin. Pharmacol. Ther. · Nov 1993
Randomized Controlled Trial Clinical TrialKetoprofen, acetaminophen plus oxycodone, and acetaminophen in the relief of postoperative pain.
Ketoprofen (Orudis) is a nonsteroidal anti-inflammatory drug that is currently approved in the United States for the management of mild to moderate pain. The objective of this trial was to determine the effectiveness of orally administered ketoprofen in the management of severe postoperative pain. This randomized, double-blind parallel study compared the efficacy and safety of single doses of 100 mg or 50 mg ketoprofen, the combination of 650 mg acetaminophen plus 10 mg oxycodone hydrochloride, 650 mg acetaminophen, or placebo in 240 patients with severe postoperative pain after cesarean section. ⋯ Remedication time for the group receiving 100 mg ketoprofen was significantly longer than for the other treatment groups. Significantly more patients who took repeated doses of the combination (84%) than those who took either dose of ketoprofen (70%) had adverse effects. Ketoprofen at both dose levels was shown to be effective, long-lasting, and well tolerated, and it should be considered as a viable option for the management of moderate to severe postoperative pain.