Effects of an orally active renin inhibitor, Ro 42-5892, in patients with essential hypertension.

Ro 42-5892 (Ro) is a new renin inhibitor that has been shown to be an orally effective compound in primates and in the first exploratory studies in humans. However, no firm conclusions could be drawn from the human trials and therefore the present study was designed to evaluate the antihypertensive efficacy of the compound in a double-blind, placebo-controlled trial. After a 3 week wash-out period and a 1 week single-blind placebo period, 24 patients were randomized to receive once daily orally either placebo or 600 mg Ro 42-5892 (N = 12/group) for 8 days. On the last day of treatment, an intravenous infusion of placebo or 100 mg Ro was given in a double-blind fashion, 4 h after the oral administration. Blood pressure (BP), heart rate (HR), plasma renin activity (PRA), immunoreactive renin (IRR), and plasma Ro levels were measured repeatedly on the first and last days of treatment. After the first oral intake of Ro, sitting diastolic BP dropped significantly from 30 min to 24 h post-dose when compared to placebo (-10.2 +/- 1.2 mm Hg v - 0.4 +/- 2.0 mm Hg at peak and -6.9 +/- 1.8 mm Hg v 1.7 +/- 0.9 mm Hg at trough; P < .01 respectively). The trough effects of Ro and placebo after the 7th and 8th doses were -5.1 +/- 1.6 mm Hg v -0.2 +/- 1.0 mm Hg; P < .05 and -5.4 +/- 1.3 mm Hg v 2.3 +/- 1.2 mm Hg; P < .01, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)