Antihypertensive effect of dilevalol is directly related to dose and plasma concentrations

Dilevalol is a novel antihypertensive agent combining vasodilation due to selective β 2-adrenergic receptor agonism with nonspecific β antagonism. To determine the relation of dilevalol dose and plasma concentration to antihypertensive effect, dilevalol (n = 15) or placebo (n = 3) was administered to 18 hypertensive subjects. The study was performed under blinded conditions during a 21-day hospitalization after a 3-week drug-free outpatient phase. In the 15 hypertensive patients receiving dilevalol orally in single morning doses of 200, 400 and 800 mg each for 5 days, the drug was shown to reduce blood pressure effectively for 24 hours at all doses. The antihypertensive effect was significantly related to dose administered and to the concentration of unchanged dilevalol measured in plasma. Dilevalol did not cause excessive changes in heart rate at rest and did not produce postural hypotension. The antihypertensive effectiveness of dilevalol was essentially the same after the first and fifth (steady state) doses at each dose level. Finally, no tendency toward rebound hypertension or tachycardia was observed after the abrupt discontinuation of dilevalol in these patients.