Effects of Repeated Oral Administration of Renin Inhibitor ES-8891 on the Renin-Angiotensin System in Human Subjects

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Repeated oral doses (120mg or 240mg, once daily) of the human renin inhibitor ES-8891 were given for 10 days to 16 normotensive male subjects on a normal sodium diet. Both doses produced significant inhibition of plasma renin activity (complete inhibition at 0.5 and 1 hour, 50% inhibition at 2 hours) which was inversely correlated with the plasma level of ES-8891. Plasma immunoreactive active renin was not enhanced in spite of significant decreases in plasma angiotensin I and aldosterone levels. There was no significant change in blood pressure or heart rate. No adverse reactions were evident. These results suggest that ES-8891 is an orally active human renin inhibitor which may be clinically useful. (Hypertens Res 1992; 15: 41-44)