European journal of clinical pharmacology
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Eur. J. Clin. Pharmacol. · Jan 1991
Randomized Controlled Trial Clinical TrialHemodynamic effects of Ro 23-6152 in patients with essential hypertension.
In a double blind study 8 patients with uncomplicated essential hypertension received in random order single oral doses of placebo and 10, 30 and 80 mg Ro 23-6152, a novel calcium entry blocker, on 4 different days. Patients were assessed 15 min before dosing and at several time intervals over the following 6 h. Ro 23-6152 30 and 80 mg induced a significant decrease (mean maximum 7 mmHg.1-1.min-1) in total peripheral resistance, while cardiac output, stroke volume and heart rate were slightly increased (mean maximum 0.51.min-1, 10 ml, 5 beats.min-1, respectively) but not significantly so. ⋯ The PQ interval was also non-significantly increased by no more than 20 ms. It appears that the main hemodynamic effect of Ro 23-6152 in hypertensive patients is a decrease in peripheral resistance. The antihypertensive effect, at least in this short term study, was only modest, probably because the fall in peripheral resistance was partly compensated by an increase in cardiac output.
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Eur. J. Clin. Pharmacol. · Jan 1991
Single and multiple dose pharmacokinetics of etizolam in healthy subjects.
The pharmacokinetics of etizolam, a new thienodiazepine derivative, has been examined after single and multiple (0.5 mg tablet) (0.5 mg b.d for 1 week) oral therapeutic doses in healthy volunteers. The single-dose kinetic profile of etizolam suggested that absorption after oral dosage was reasonably rapid, the maximum plasma concentration (Cmax) being attained within 0.5-2 h in all subjects. The mean elimination half-life (t1/2) averaged 3.4 h. ⋯ At steady state plasma concentrations of the main metabolite, alpha-hydroxyetizolam, were higher and disappeared more slowly (mean t1/2 8.2 h) than those of the parent compound. Taken with the fact that in animals the metabolite shows almost the same potency of pharmacological action as etizolam, this suggests that it may contribute significantly to the clinical effects of the parent compound. Based on the kinetic characteristics of the parent drug and its metabolite, etizolam can be regarded as a short-acting benzodiazepine, with elimination kinetics between those of short-intermediate derivatives and ultra-rapidly eliminated benzodiazepines.
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Eur. J. Clin. Pharmacol. · Jan 1990
Clinical pharmacokinetics of intravenous and oral 9-amino-1,2,3,4-tetrahydroacridine, tacrine.
The pharmacokinetics of 9-amino-1,2,3,4-tetrahydroacridine; tacrine, THA, was studied after intravenous administration and following the first and last oral doses of a seven week clinical trial involving 8 patients with amyotrophic lateral sclerosis, ALS. Two surgical patients given intravenous THA for reversal of postoperative sedation were also included. Plasma concentration of THA and in some cases the metabolite, 1-hydroxy-THA, were assayed using a selective and sensitive method with high performance liquid chromatography. ⋯ After seven weeks treatment with oral THA, plasma concentrations immediately prior to medication were below 10 ng/ml in three patients and above 100 ng/ml in two patients. At the same occasion the plasma metabolite concentrations considerably exceeded those of THA. THA medication was associated with side effects in the majority of the patients.
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Eur. J. Clin. Pharmacol. · Jan 1989
Inaccuracy in the doses of injectable medications dispensed from rubber-stoppered vials.
The literature of pharmacology often assumes that a full dosage is utilized when the contents of a vial have been administered by syringe. Five hundred discarded medication vials were assayed. The residues amounted to 1.98% to 8.81% of the listed dosages. ⋯ Although the amount of drug lost during preparation and administration may be of little therapeutic consequence, the discrepancy between intended and administered dosage is reflected in economic loss and pharmacological confusion. Pharmacological data should be adjusted for such losses. Medication wastage could be reduced by redesign of vials and alterations in practice of the administration.
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Eur. J. Clin. Pharmacol. · Jan 1989
Randomized Controlled Trial Clinical TrialEffects of clobazam and clonazepam on saccadic eye movements and other parameters of psychomotor performance.
The effects of two benzodiazepine anticonvulsants clobazam (20 mg) and clonazepam (2 mg) in a variety of psychomotor performance tests were compared in a placebo controlled double-blind acute oral dose study in ten healthy volunteers. Assessments included critical flicker fusion (CFF) threshold, the Sternberg memory scanning and choice reaction time (CRT), peak saccadic velocity (PSV) and visual analogue scales, all previously shown to be sensitive to the effects of benzodiazepines. ⋯ Clonazepam significantly increased memory scanning time compared to clobazam. Clobazam was remarkably free of cognitive and psychomotor side-effects.