Fosinopril, a phosphinic acid inhibitor of angiotensin I converting enzyme: in vitro and preclinical in vivo pharmacology.

Journal of Cardiovascular Pharmacology
J M DeForrestD W Cushman

Abstract

Fosinopril is the first member of a new chemical class of angiotensin I (AI) converting enzyme (ACE) inhibitors, the phosphinic acids. In vitro, SQ 27,519, the active moiety of the prodrug fosinopril, was a more potent inhibitor of purified rabbit lung ACE- (IC50 = 11 vs. 23 nM) and bradykinin-induced contractions of guinea pig ileum than captopril. In vivo, SQ 27,519 was equipotent to captopril as an inhibitor of an AI pressor response after intravenous (i.v.) administration to conscious rats and monkeys but appeared to be less potent in conscious dogs. After oral administration, fosinopril again was equipotent to captopril as an inhibitor of an AI pressor response in rats and monkeys and slightly less potent in dogs. However, both SQ 27,519 (i.v. studies) and fosinopril (oral studies) had a longer effect than captopril in all three species. When fosinopril was administered orally for 5 days, its effects on an AI pressor response were the same on days 1 and 5, suggesting lack of tolerance to the compound. The ACE inhibitory effect of captopril, but not fosinopril, was prolonged in conscious rats with glycerol-induced acute renal failure, suggesting that fosinopril is excreted by an extrarenal route. Finally, fosinopril had no ...Continue Reading

Citations

Apr 29, 1998·Journal of Clinical Pharmacology·O Y HuK M Chu
Jan 1, 1993·European Journal of Clinical Pharmacology·T W GehrK L Duchin
Jan 1, 1992·Fundamental & Clinical Pharmacology·M GrimaJ L Imbs
Jul 6, 2014·Drug Discovery Today·Katarzyna RegulskaMarek Murias
Sep 8, 2018·Chemical Reviews·Allie Y ChenSeth M Cohen
Sep 6, 2014·Organic Letters·Heather J JohnstonAlison N Hulme

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