CERANAPRIL (SQ-29,852), AN ORALLY ACTIVE INHIBITOR OF ANGIOTENSIN CONVERTING ENZYME (ACE)

Ceranapril (SQ 29,852) is a new inhibitor of angiotensin I (AI) converting enzyme (ACE) belonging to the hydroxylphosphonate class. The purpose of the present report is to present the in vivo pharmacology of ceranapril in conscious animal models. In conscious, normotensive rats, ceranapril administered i.v. (ED50 = 63 nmol/kg) or p.o. (ED50 = 530 nmol/kg) inhibited an AI pressor response with potency equal to that of captopril. However, in conscious dogs, ceranapril was a relatively poor inhibitor of the AI pressor response after both i.v. (ED50 = 300 nmol/kg) and p.o. (ED50 = 18 μmol/kg) administration; in monkeys ceranapril was a good inhibitor of the AI pressor response after i.v. (ED50 = 60 nmol/kg) but not p.o. (ED50 = 18 μmol/kg) administration. In rats, the duration of ceranapril's inhibition of an AI pressor response was longer than an equimolar dose of captopril. Similarly, in SHR, ceranapril's blood pressure lowering effect had a longer duration than that of captopril. Ceranapril's ACE inhibitory effects were longer lasting in anephric rats than in sham rats, suggesting a renal route of excretion for ceranapril. Ceranapril administration to conscious female dogs resulted in significant increases in renal plasma flow and GFR. In SHR, doses of 23 and 68 μmol/kg resulted in significant blood pressure lowering that lasted 24 h. Oral doses of 2.3, 6.8, 23, and 68 μmol/kg in two-kidney, one-clip hypertensive rats resulted in significant and dose-related falls in arterial pressure, which again persisted for 24 h. Finally, in two-kidney perinephritic hypertensive monkeys, 15 μmol/kg of p.o. ceranapril lowered arterial pressure from 152 ± 15 to 80 ± 12 mm Hg. It is concluded that ceranapril is an effective inhibitor of ACE, although its in vivo potency is species dependent.