EFFICACY AND TOLERABILITY OF THE RENIN INHIBITOR RO-42-5892 IN PATIENTS WITH HYPERTENSION

The efficacy of multiple oral administration of the renin inhibitor Ro 42-5892 )-3-cylopropyl-2,3-dihydroxypropyl]-imidazole-4-pr opionamide ] was studied. Forty-nine patients with moderate essential hypertensio n were randomly assigned to three groups that entered an 8-day double- blind oral treatment period: daily administration of placebo (group A) , 300 mg Ro 42-5892 (group B), or 600 mg Ro 42-5892 (group C). Four ho urs after the last oral drug intake, placebo was administered intraven ously to subjects in group A and 100 mg Ro 42-5892 was administered in travenously to subjects in groups B and C. Sitting systolic and diasto lic blood pressures were measured on days 1 and 8 with a blood pressur e device. On day 1, systolic blood pressure maximally decreased by 13. 3 +/- 9.3, 20.2 +/- 11.2, and 24.1 +/- 11.3 mm Hg in groups A, B, and C, respectively (mean +/- SD; p < 0.01 for group A versus group C). Di astolic blood pressure maximally decreased 9.4 +/- 5.7, 13.9 +/- 8.7, and 11.8 +/- 5.7 mm Hg (difference not significant). On day 8, systoli c blood pressure maximally decreased 19.5 +/- 16.5, 26.5 +/- 17.4, and 30.5 +/- 18.4 mm Hg and diastolic blood pressure maximally decreased 14.8 +/- 5.0, 16.2 +/- 9.0, and 17.9 +/-12.7 mm Hg (difference not sig nificant) compared with pretreatment values. Intravenous drug administ ration did not further reduce blood pressure, suggesting that the mode of action and not the low bioavailability was the limiting factor for the low efficacy.