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  • Title: Antiarrhythmic significance of dosing intervals in beta receptor blocking therapy of hypertension with acebutolol.
    Author: Frick MH, Kala R.
    Journal: Am J Cardiol; 1981 Nov; 48(5):911-6. PubMed ID: 6118059.
    Abstract:
    Six hypertensive patients with daily ventricular arrhythmias underwent a double-blind crossover study to examine whether a once daily regimen of beta receptor blockade was equipotent in antihypertensive and antiarrhythmic activity to a twice daily regimen. Acebutolol, a relatively cardioselective beta blocking compound with intrinsic sympathomimetic properties, was given in two regimens: 200 mg twice daily or 400 mg once daily. Ventricular ectopic beats were analyzed both during physical exercise and with multiple 24 hour ambulatory electrocardiographic (Holter) recordings. Serum concentrations of acebutolol and its acetyl metabolite were determined using high pressure liquid chromatography. The two regimens of acebutolol were equally potent in reducing the blood pressure and heart rate at rest and during physical exertion. The hourly heart rates during 24 hours were reduced to the same extent by both regimens. The single daily 400 mg dose did not significantly reduce the incidence of arrhythmias, whereas 200 mg twice daily evoked a significant reduction during 24 hours. Serum concentrations of acebutolol were twice as great with the twice daily regimen as with the single dose. Both treatments significantly shortened the Q-Tc interval. The data suggest that, despite apparent beta receptor blockade and good blood pressure control, beta blocking agents with a relatively short plasma half-life lose their antiarrhythmic potency when administered on a once daily basis. This property seems to be more related to the plasma concentration of the compound than to the degree of clinically assessed beta receptor blockade.
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