HUMORAL AND HEMODYNAMIC-EFFECTS OF IDRAPRIL CALCIUM, THE PROTOTYPE OFA NEW CLASS OF ACE-INHIBITORS, IN ESSENTIAL HYPERTENSIVE PATIENTS

Idrapril is the prototype of a new class of ACE inhibitors, characteri sed by the presence of a hydroxdmic group. Six untreated in-patients w ith essential hypertension were given single oral doses of the calcium salt of idrapril, idrapril calcium (200 mg) and placebo according to a double blind, randomised experimental design. Supine and upright blo od pressure, heart rate, plasma idrapril serum ACE, active renin and a ngiotensin II were measured at timed intervals for 24 hours after dosi ng. Plasma idrapril reached a peak after 2 hours (3.01 mu g . ml(-1)), and by 12 hours the compound had al most disappeared (67 ng . ml(-1)) . Derived t(1/2) was 1.4-2.2 h. ACE activity was suppressed [from 77.9 to 3.3 after 2 hours and 11.8 after 12 hours nmol(-1). min(-1). ml] a nd angiotensin II production inhibited [from 8.8 to 3.1 (after 1 hour) and 7.5 (after 12 hours) pg . ml(-1)] for up to 12 h, while active re nin rose up to 24 h [from 12.3 to 20.1 (after 8 hours) and 17.5 (after 24 hours) pg ml(-1)]. Compared to placebo, idrapril calcium significa ntly lowered both supine blood pressure starting at 4 hours (idrapril calcium 140/93 mmHg; placebo 157/101 mmHg) up to 24 hours (idrapril ca lcium 142/91 mmHg; placebo: 155/97 mmHg), and upright blood pressure s tarting at 3 hours (idrapril calcium 135/95 mmHg; placebo 147/100 mmHg ) up to 24 hours (idrapril calcium 132/92 mmHg; placebo 145/100 mmHg). Idrapril calcium appears to be an effective ACE inhibitor in essentia l hypertension, with a hypotensive action for up to 24 h.