Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Oct 1987
Comparative Study Clinical Trial Controlled Clinical TrialPharmacokinetics and pharmacodynamics of vecuronium administered by bolus and infusion during halothane or balanced anesthesia.
Vecuronium was administered to two patient groups as a single intravenous dose, 60 micrograms/kg, combined with an infusion, 1 microgram/min/kg. Anesthesia was maintained for the first group with a halothane-nitrous oxide technique; the second group received fentanyl-barbiturate-tranquilizer-nitrous oxide. As the infusion ended, plasma vecuronium concentrations were 0.34 (+/- 0.10) microgram/ml for the halothane group and 0.32 (+/- 0.07) microgram/ml for the fentanyl group, associated with 93% (+/- 8) and 88% (+/- 10) twitch depression, respectively. ⋯ For the halothane group the steady-state volume was 0.21 (+/- 0.04) L/kg, the clearance was 2.9 (+/- 0.1) ml/min/kg, and the elimination half-life was 100 (+/- 36) minutes; for the fentanyl group these were 0.20 (+/- 0.08) L/kg, 3.2 (+/- 0.1) ml/min/kg, and 84 (+/- 43) minutes, respectively. Plasma concentrations associated with 50% blockade averaged 0.2 microgram/ml for both groups. Neither the pharmacokinetics nor the pharmacodynamics of vecuronium in humans differed between these two patient groups.
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Clin. Pharmacol. Ther. · Aug 1987
Randomized Controlled Trial Comparative Study Clinical TrialComparison of intramuscular dezocine with butorphanol and placebo in chronic cancer pain: a method to evaluate analgesia after both single and repeated doses.
Sixty hospitalized subjects with chronic moderate to severe pain as a result of advanced cancer were enrolled in a randomized, parallel, double-blind trial comparing single doses and multiple doses of intramuscular dezocine (10 mg) with butorphanol (2 mg) and placebo. During the initial 6-hour efficacy evaluation, analgesia was measured using verbal and visual scriptors and vital signs, and acute toxicity information was recorded. Subjects with initial pain relief entered the 7-day multidose portion of the trial, and efficacy and toxicity data were recorded daily. ⋯ Dezocine had less toxicity than had butorphanol after both single and repeated doses, further suggesting that dezocine may be beneficial in managing chronic cancer pain. The described study design is unique in that it compares the analgesic efficacy and toxicity of several analgesics with placebo after both single and multiple doses in the same subject. This method may prove to be an alternative pain model to evaluate chronic cancer pain.
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Clin. Pharmacol. Ther. · May 1987
Randomized Controlled Trial Comparative Study Clinical TrialKetorolac tromethamine as compared with morphine sulfate for treatment of postoperative pain.
Ketorolac tromethamine, a nonnarcotic, prostaglandin synthesis-inhibiting analgesic, was compared with morphine sulfate for relief of moderate to severe postoperative pain. The 155 patient participants received single intramuscular doses of either ketorolac, 10, 30, or 90 mg, or morphine, 6 or 12 mg, administered in a double-blind, randomized fashion. Pain scores (verbal and visual analog) were recorded at baseline and assessed at 30 minutes and then hourly to 6 hours. ⋯ There were no serious side effects reported. The only side effect reported in more than 3% of patients was 8% somnolence with morphine. This study shows ketorolac to be a safe and effective analgesic for relief of postoperative pain.
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Clin. Pharmacol. Ther. · Nov 1986
Clinical Trial Controlled Clinical TrialProlonged blockade of opioid effect with oral nalmefene.
In a placebo-controlled, double-blind study we evaluated the ability of a single 50 mg oral dose of nalmefene to block the effects of intravenous opioid challenge (2 micrograms/kg fentanyl). Fentanyl-induced respiratory depression (CO2 responsiveness), analgesia (tourniquet ischemia), and subjective effects were totally blocked for 48 hours and showed only minimal breakthrough 72 hours after nalmefene. Plasma concentration-time data for nalmefene indicate good oral bioavailability and a prolonged terminal elimination phase (mean t1/2 11.1 hours). These findings suggest that nalmefene could provide prolonged effectiveness in limiting emergence of opioid effects during addiction therapy.