Dose-response relations with
penbutolol--a
beta-adrenergic blocking agent--were evaluated in a double-blind multiclinic study conducted in 302 outpatients with mild to moderate
hypertension (untreated supine diastolic blood pressure [BP] greater than or equal to 95 and less than or equal
to 115 mm Hg).
Penbutolol was administered once daily in 10, 20 or 40 mg doses for 6 weeks and compared with placebo. Mean declines from baseline in supine diastolic BP were comparable in the 3
penbutolol treatment groups and significantly superior to placebo (p less than 0.05). A significant difference between
penbutolol dosage groups was observed only for supine systolic BP; the mean decline at 20 mg/day was significantly larger than that
at 10 mg/day (p less than 0.05). Maximum BP response developed in approximately 4 weeks
at 10 mg/day and in 2 weeks at the higher dosages. Decline in mean heart rate after 6 weeks of
penbutolol therapy significantly exceeded placebo only at 40 mg/day (7.2 vs 2.5 beats/min, p less than 0.05). Treatment was well-tolerated and discontinued because of adverse effects in only 7 patients receiving
penbutolol and 3 receiving placebo. The lack of significant
bradycardia and the low incidence of other troublesome adverse effects are potential advantages during
antihypertensive therapy with
penbutolol. With rapid onset of effect and good efficacy and tolerability, the 20 mg once-daily dose appears to be optimum for
therapy with this new agent.