Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Aug 1995
Randomized Controlled Trial Clinical TrialCentral nervous system effects of subdissociative doses of (S)-ketamine are related to plasma and brain concentrations measured with positron emission tomography in healthy volunteers.
Plasma concentrations, maximum regional brain concentrations, and specific regional binding in the brain after administration of 0, 0.1, and 0.2 mg/kg doses of (S)-ketamine were measured in a randomized, double-blind, crossover study in five volunteers and were related to induced effects such as analgesia, amnesia, and mood changes. Specific binding in the brain was assessed by simultaneous administration of (S)-[N-methyl-11C]ketamine quantified by positron emission tomography. ⋯ Memory impairment and psychotomimetic effects were related to dose, plasma concentration 4 minutes after administration, and decreased regional binding of (S)-ketamine in the brain and were consistently seen at plasma and maximum regional brain (S)-ketamine concentrations higher than 70 and 500 ng/ml, respectively. The magnitude of specific binding of (S)-ketamine, measured with positron emission tomography, can be related directly to drug effects.
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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).