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RHC 3659: a new orally active angiotensin converting enzyme inhibitor in normal volunteers.
Author(s) -
Burnier M,
Turini GA,
Brunner HR,
Porchet M,
Kruithof D,
Vukovich RA,
Gavras H
Publication year - 1981
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1981.tb01327.x
Subject(s) - captopril , aldosterone , plasma renin activity , angiotensin converting enzyme , renin–angiotensin system , endocrinology , enzyme inhibitor , medicine , angiotensin ii , chemistry , ace inhibitor , renin inhibitor , oral administration , blood pressure , enzyme , biochemistry
1 The new converting enzyme inhibitor RHC 3659 was tested in 15 male volunteers. The study consisted of two parts: first, the ability of a single oral dose (5, 10, 20, 40 or 80 mg) to inhibit the pressor response to exogenous angiotensin I was tested with blood pressure and heart rate monitored continuously through an intraarterial catheter. A dose‐related shift to the right of the pressor response curve to angiotensin I was observed with a peak occurring within 0.5 to 1 h. The pressor response to angiotensin II was unaffected. 2 In the second part, plasma renin and converting enzyme activity, angiotensin II and aldosterone were measured serially before and up to 8 h after administration of a single oral dose of RHC 3659. As expected. plasma angiotensin II and aldosterone fell within 30 min while plasma renin activity increased. Plasma converting enzyme activity was suppressed at 0.5 h in a dose‐related manner with levels still below 30% of control 4 h following 80 mg of the inhibitor. 3 However, in vitro the enzyme‐ inhibitor complex seemed quited fragile since during storage of the plasma samples at −20 degrees C, converting enzyme activity increased significantly already within days (P less than 0.001, n = 28) and continued to rise for more than 2 months. This fragility may explain the seemingly lower potency of RHC 3659 when compared to captopril. No side effects were observed.