Responses to an orally active renin inhibitor, remikiren (Ro 42-5892), after controlled salt depletion in humans.
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MacFadyen RJ, Jones CR, Doig JK, Birnbock H, Reid JL
Responses to an orally active renin inhibitor, remikiren (Ro 42-5892), after controlled salt depletion in humans.
J Cardiovasc Pharmacol. 1995 Mar;25(3):347-53.
- PubMed ID
- 7769797 [ View in PubMed]
- Abstract
The biological effects of dose-dependent inhibition of renin have rarely been extensively studied after oral (p.o.) dosing in humans. We studied remikiren (Ro42-4892), a selective renin inhibitor, in normal volunteers after activation of the renin-angiotensin system (RAS) based on salt depletion. Twelve normal men (28 +/- 9 years, 77 +/- 10 kg), comprising three consecutive dose panels of 4 subjects, received four treatments, double-blind and randomised 2 weeks apart: panel I, placebo (P), or 30, 100, and 300 mg, remikiren; panel II, placebo or 300, 600 mg, 1,000; panel III, placebo or 30, 600, and 1,000 mg. The RAS was activated by 40 mmol/day sodium diet plus frusemide (40 mg BDS), for 3 days before each study day. Data (mean +/- SD) were examined by repeated-measures analysis of variance (ANOVA). RAS activation was confirmed by 24-h urinary sodium excretion (screen, 142 +/- 74 mmol/24 h; prestudy, 66 +/- 33, 59 +/- 41, 78 +/- 4, 73 +/- 30 mmol/24 h) and increase in plasma renin activity (PRA) (screen, 0.8 +/- 0.3 ng AI/ml/h; before dosing, P, 6.5 +/- 3.1; 30 mg, 8.2 +/- 3; 100 mg, 9.4 +/- 5.7; 300 mg, 6.5 +/- 2.4; 600 mg, 5.2 +/- 2; 1,000 mg, 6.2 +/- 4.4 ng AI/ml/h).(ABSTRACT TRUNCATED AT 250 WORDS)