Plasma clearance, volumes of distribution, and renal and extrarenal clearances of digoxin were calculated from plasma digoxin concentrations and urinary excretion of digoxin after intravenous injection of digoxin in 8 subjects. The investigation was repeated in the same subjects during long-term treatment with spironolactone. Increased plasma concentration of digoxin was detected during spironolactone treatment. Calculated plasma and renal clearances of digoxin and the volumes of distribution decreased statistically significant. Near maximal capacity for the tubular secretion of digoxin was found when normal digoxin dosage was used. It is suggested that unless spironolactone decreases the myocardial sensitivity for digoxin, the loading dose as well as the maintenance dose of digoxin should be reduced during treatment with spironolactone.
In a double-blind randomised group comparative trial the adverse effects of the {3blockers acebutolol and metoprolol were compared in patients with arterial hypertension. The patients were asked before and during treatment about a number of complaints/ symptoms, known to be common adverse reactions to {3-blockers. A total of 215 patients were randomised, and 82 in each group completed 16 weeks' treatment. No statistically significant differences were found in the reduction in blood pressure and heart rate, and confidence limits excluded major differences. After 4 weeks the heart rate was reduced more in the metoprolol group than in the acebutolol group. Before and after 16 weeks' treatment no differences were found in either the number of patients with complaints/ symptoms or in the severity of these complaints. Both parameters were reduced evenly during the study. Patients receiving metoprolol complained more often of palpitations 4 weeks after the start of treatment. Our results indicate that the choice between acebutolol and metoprolol should not be based on therapeutic efficacy or on adverse effects.
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