Penbutolol (Hoe 893d) in primary hypertension. Blood pressure effects, tolerance and plasma concentrations

Penbutolol (Hoe 893d), a long-acting non-selective beta-adrenoceptor blocking agent, was given once daily to 23 patients with primary hypertension, WHO Stages I-II. The dose (50-100mg) needed to achieve the therapeutic goal, i.e. supine diastolic BP less than 95 mm Hg, was titrated individually. On a daily dose of penbutolol 83 +/- 19 mg (mean +/- SD) blood pressure (BP, mean +/- SD) fell from 180 +/- 21/112 +/- 8 mmHg on placebo to 154 +/- 25/94 +/- 14 mmHg. 18 patients who reached the therapeutic goal (responders) continued in a double blind, cross-over study versus placebo, during which the supine BP fell on average 20/10 mmHg on the same dose of penbutolol, and 2/1 mmHg on placebo. Plasma concentrations (mean +/- SD) of free 0.10 +/- 0.07 microgram/ml) and total (2.02 +/- 1.39 microgram/ml) penbutolol did not differ between responders and nonresponders, and were not correlated with the fall in BP. Side effects were mild and mostly well tolerated. One patient developed dermatitis and another an elevation of liver enzymes.