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 · 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 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.
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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 · Oct 1982
Randomized Controlled Trial Clinical TrialCodeine added to paracetamol induced adverse effects but did not increase analgesia.
1 In a double-blind crossover study identical oral surgical procedures were performed on two separate occasions in 24 outpatients. 2 At one operation they were given tablets containing paracetamol + codeine phosphate (400 mg + 30 mg), and at the other plain paracetamol (400 mg). The day of operation 2 tablets were taken 3, 6 and 9 h after surgery, the following two days 1 tablet four times daily. 3 Several measurements/assessments were recorded for a paired comparison of the postoperative courses. 4 No increase In the analgesic effect could be demonstrated by addition of codeine to paracetamol. 5 On the day of operation 18 patients reported adverse effects like nausea, dizziness and drowsiness with paracetamol + codeine, while only 3 patients experienced side effects with paracetamol alone (P less than 0.001). 6 Measurements revealed almost identical swelling after the two operations. 7 Compared with results obtained in previous studies, the present findings indicate that paracetamol may exert anti-inflammatory activity and reduce postoperative swelling, even when given 3 h after surgery. 8 On the day of operation and the following two days 20 patients preferred the treatment with plain paracetamol, while only 4 favoured paracetamol + codeine (P less than 0.001).