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 1991
Pitfalls of pharmacokinetic dosage guidelines in renal insufficiency.
As the renal elimination of most drugs is closely correlated with the endogenous creatinine clearance, it is possible to use this parameter of kidney function to adjust drug dosage in renal failure. However, this simple procedure neglects possible changes in the volume of distribution, plasma protein binding, drug metabolism, intestinal absorption, and pharmacodynamics in renal insufficiency, as well as the occurrence of biologically active drug metabolites. Because of these uncertainties in critical cases the validity of the dosage calculated using the creatinine clearance should be checked by clinical surveillance and measurements of drug blood concentrations. Further, pharmacokinetic dosage guidelines based on the individual creatinine clearance may not be applicable to diuretics and drugs which have markedly differing kinetics of pharmacodynamic effects and blood levels.
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Eur. J. Clin. Pharmacol. · Jan 1991
Randomized Controlled Trial Clinical TrialTransdermal fentanyl for the treatment of pain after major urological operations. A randomized double-blind comparison with placebo using intravenous patient-controlled analgesia.
Transdermal fentanyl 75 micrograms/h (Fentanyl-TTS) was compared with placebo in a randomized double-blind study in the early postoperative period, using 50 patients recovering from major urological operations. Analgesic efficacy was individually titrated with intravenous fentanyl by means of a PCA pump (demand dose 34 micrograms, lockout time 5 min). The test systems were applied 8 h before anaesthesia and were left in situ for 24 h. ⋯ Patient acceptance was high in both groups. Side-effects were of only minor intensity and did not differ between the two groups. In particular, there was no case of clinically relevant respiratory depression.