Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Aug 1995
Pharmacokinetics and pharmacodynamics of rocuronium at the vocal cords and the adductor pollicis in humans.
The pharmacokinetic-pharmacodynamic relationship of rocuronium at the laryngeal adductor muscles and the adductor pollicis was determined in eight patients during general anesthesia. Rocuronium was administered as an infusion at a rate of 100 micrograms.kg-1.min-1 over 5 minutes. The half-life of transport between plasma and biophase (effect compartment) was significantly shorter at the adductor laryngeal muscles (2.7 +/- 0.6 minutes, mean +/- SD) than at the adductor pollicis (4.4 +/- 1.5 minutes, p = 0.003). ⋯ L-1) than at the adductor pollicis (823 +/- 157 micrograms. L-1, p = 0.0001). The shorter onset of neuromuscular blockade at the laryngeal muscles than at the adductor pollicis may be explained by a faster transfer rate at the laryngeal adductor muscles neuromuscular junction than at the adductor pollicis neuromuscular junction.
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Clin. Pharmacol. Ther. · Aug 1995
The in vitro degradation of cisatracurium, the R, cis-R'-isomer of atracurium, in human and rat plasma.
To assess the mechanism and rate of in vitro degradation of cisatracurium in aqueous buffer and in human and rat plasma. ⋯ In human plasma the rate-limiting step in the degradation of cisatracurium is Hofmann elimination, with the initial formation of a monoquaternary acrylate. The observation that the monoquaternary alcohol results from ester hydrolysis of the monoquaternary acrylate by plasma esterase(s) explains the presence of the monoquaternary alcohol metabolite in human plasma during clinical studies with cisatracurium. The rapid hydrolysis of cisatracurium by rat plasma relative to human indicates a major species difference in plasma esterase(s).
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To describe the pharmacokinetics of midazolam, a water-soluble benzodiazepine with a short half-life, in critically ill neonates. ⋯ The mean midazolam doses required for critically ill neonates are lower than those required for older infants.
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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.