Effects of carvedilol on blood pressure in patients with mild to moderate hypertension. A dose response study.

Carvedilol 12.5, 25 and 50 mg was administered once daily for 4 weeks to patients with mild to moderate hypertension. The purpose of the study was to investigate the antihypertensive action of carvedilol when administered once daily and to investigate the pharmacokinetics of carvedilol in patients with mild to moderate hypertension. Measurable decreases in blood pressure (BP) occurred within 1 hour after the first dose. Peak decreases in supine diastolic blood pressure (DBP) were 9.0 +/- 6.8, 15.5 +/- 6.7, 14.7 +/- 10.6 and 22.5 +/- 7.6mm Hg (+/- SD) for the placebo, 12.5, 25 and 50mg carvedilol groups, respectively, and occurred between 3 and 7 hours after the dose. Administration of carvedilol once daily for 4 weeks kept supine DBP below baseline levels for 24 hours. Trough supine DBP after 4 weeks of treatment were 0.6 +/- 6.5, 7.3 +/- 7.9, 8.8 +/- 7.4 and 12.1 +/- 3.8mm Hg (+/- SD) below baseline. Serum levels of carvedilol were proportional to the dose. Peak serum levels were 39 +/- 27, 75 +/- 38 and 161 +/- 131 mu/L for carvedilol 12.5, 25 and 50mg. The kinetics of carvedilol did not change with repeated administration. Carvedilol was well tolerated; 2 patients experienced dizziness associated with postural hypotension after administration of the 50mg dose. Carvedilol 12.5, 25 and 50mg effectively reduced BP for 24 hours when administered once daily.