Beta-blocking potency and electrophysiologic effects of acebutolol.
The beta-blocking potency of three doses of acebutolol (100, 200, and 600 mg three times a day) has been compared to that of propranolol (30, 60, and 180 mg three times a day) in a double-blind crossover study in 10 healthy volunteers (seven men, three women). On the basis of reduction in resting and exercise heart rates, propranolol was three to four times more potent than acebutolol on a milligram-for-milligram basis. Plasma levels showed large interindividual variation for both agents. Plasma levels were weakly correlated with the degree of beta blockade for both acebutolol (r = 0.333, p less than 0.001) and propranolol (r = 0.381, p less than 0.01). Dose and percent beta blockade were more strongly correlated (propranolol, r = 0.503, p less than 0.001; acebutolol, r = 0.574, p less than 0.001). In 11 patients (10 men, one woman) with coronary artery disease, acebutolol at 1 mg/kg infused over 15 minutes decreased heart rate and slowed conduction, increased the refractoriness of the atrioventricular node without a significant change in the atrial refractoriness, and at plasma levels greater than or equal to 1000 ng/ml slowed His-Purkinje conduction. The comparative potency data suggest that the magnitude of the decrease in the resting and exercise-induced changes in heart rate and double product, in relation to dose of acebutolol, provides quantitative indices for judging adequacy by beta blockade in clinical therapeutics. The use of plasma drug levels, however, does not appear to be helpful in judging the adequacy of beta blockade.(ABSTRACT TRUNCATED AT 250 WORDS)
Singh
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Williams
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Harrison
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D000070:Acebutolol / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D001283:Atrioventricular Node / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy; D004594:Electrophysiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use
D000319:Adrenergic beta-Antagonists; D000070:Acebutolol; D011433:Propranolol