British journal of clinical pharmacology
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Br J Clin Pharmacol · Nov 1983
Active metabolites of acenocoumarol: do they contribute to the therapeutic effect?
The pharmacokinetics and pharmacodynamics of racemic acenocoumarol (AC), the amino (AM) and acetamido (AA) derivative were investigated in healthy volunteers after administration of a single oral (10 mg) dose. All three coumarins were rapidly absorbed from the gastrointestinal tract. The elimination half-lives were 10.9, 10.4, and 4.1 h, for AC, AM and AA, respectively. ⋯ The oral administration of AC resulted in a rise in prothrombin time with a maximum effect at 24 to 30 h. No anticoagulant activity was observed upon the administration of AM and AA. The results indicate that the compounds AM and AA, if they are formed out of AC at all, do not contribute to the anticoagulant activity of AC.
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Br J Clin Pharmacol · Nov 1983
The analgesic effect of the GABA-agonist THIP in patients with chronic pain of malignant origin. A phase-1-2 study.
Fourteen patients with chronic pain of malignant origin were treated with escalating doses of THIP intramuscularly 5-30 mg in an open phase 1 study. Analgesic activity was demonstrated in 60% of the patients at the level of 20 mg THIP and a dose response relation was present. Side effects, sedation, dizziness, euphoria, nausea, and blurred vision were present in up to 80% of the patients and were dose limiting. ⋯ Mean t1/2 was 1.52 +/- 0.63 h and the clearance was 0.49 +/- 0.181 min. Significant correlations were demonstrated between serum concentration, dose of THIP, analgesic effect and side effects. It is concluded that THIP cannot be used for the treatment of chronic cancer pain, not because of insufficient analgesic effect but because of unacceptable side effects.
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Br J Clin Pharmacol · Jun 1983
Clinical Trial Controlled Clinical TrialEffects of terbutaline sulphate aerosol on bronchodilator response and lung mucociliary clearance in patients with mild stable asthma.
Ventilatory function and whole lung mucociliary clearance have been assessed in 10 patients with mild stable asthma following inhalation of 1 mg of the beta-adrenergic receptor agonist terbutaline sulphate (Bricanyl, Astra Pharmaceuticals) from a metered dose inhaler (MDI). Compared to placebo inhalation, terbutaline produced marked bronchodilatation (mean percentage increase in FEV1 14%, P less than 0.01). ⋯ The mean (+/- s.e. mean) percentage of aerosol retained in the lungs after 6 h was 58 +/- 5%, 57% +/- 5% and 57 +/- 4% for control, placebo and drug studies respectively. It is concluded that terbutaline sulphate, given as a 1 mg acute dose, does not enhance mucociliary clearance in mild stable asthmatics, although it produces marked bronchodilatation.
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Br J Clin Pharmacol · Jan 1983
Randomized Controlled Trial Comparative Study Clinical TrialA double-blind controlled clinical trial comparing fluvoxamine with imipramine.
1 The effects of fluvoxamine to a maximum of 300 mg daily were compared with those of imipramine to a maximum of 200 mg daily, in 151 patients with primary major depression. 2 Four weeks of treatment with fluvoxamine resulted in 67.2% improvement (+/- s.d. 21.6) on the Hamilton Rating Scale for Depression (26 items). Treatment with imipramine showed 62.1% improvement (+/- s.d. 29.5) on this scale. 3 Fluvoxamine had no untoward effects on the cardiovascular system, while imipramine produced systematic increases in the postural fall in blood pressure. Dry mouth, nausea, daytime somnolence and tremor were seen with fluvoxamine treatment, while imipramine was associated with dry mouth, daytime somnolence, dizziness and tremor. 4 We conclude that fluvoxamine seems to have the same general antidepressant efficacy as imipramine. It was not associated with any safety problems and was generally well tolerated.
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Br J Clin Pharmacol · Jan 1983
Randomized Controlled Trial Comparative Study Clinical TrialA double-blind placebo-controlled study of fluvoxamine and imipramine in out-patients with primary depression.
1 A double-blind placebo-controlled study of fluvoxamine and imipramine was performed in a group of depressed patients. Twenty-two patients received fluvoxamine (mean dose 101 mg/day), 25 received imipramine (mean dose 127 mg/day) and 22 received placebo. 2 Apart from an increase in the SGOT and SGPT values of four imipramine patients, no statistically significant changes in haematology or urinalysis were judged to be medically relevant. ⋯ Evaluations of the results of the Beck Depression Inventory and the Profile of Mood States revealed a statistically significant improvement for imipramine patients with respect to placebo at week 4, but not for fluvoxamine patients. It is postulated on the basis of quantitative pharmaco-EEG findings, that the slight superiority of imipramine over fluvoxamine was due to underdosing of the latter.