Pharmacokinetic and pharmacologic properties of delapril, a lipophilic nonsulfhydryl angiotensin-converting enzyme inhibitor.
Delapril is a carboxy-alkyl-dipeptide mainly converted in animals and humans to an active diacid derivative (M-I), which in turn is converted to an active 5-hydroxy-indane diacid (M-III). In humans these metabolites are excreted in the urine. The presence of the indanyl-glycine moiety gives delapril a high lipophilicity, greater than several other angiotensin-converting enzyme (ACE) inhibitors, such as captopril and enalapril. Due to its greater lipophilicity, delapril has been shown to exert a more effective inhibition of vascular ACE than captopril and enalapril, both in vitro and in vivo. The activity of delapril on tissue ACE also lasts longer than on the circulating enzyme. At doses ranging from 1-10 mg/kg orally, delapril exerts a marked and long-lasting antihypertensive action in various experimental models of hypertension. The blood pressure reduction has been shown to be accompanied by suppression of angiotensin II release from the vascular wall. In stroke-prone spontaneously hypertensive rats (SHR-SP) and in SHR with chronic renal failure, besides reducing hypertension, delapril significantly improves survival rate and prevents the development of stroke, cardiac hypertrophy, and renal sclerosis. The ability of delapril to reduce hypertrophy in vascular and cardiac tissue has been demonstrated in both in vitro and in vivo experiments.
Razzetti
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R
Research and Development Department, Chiesi Farmaceutici, Parma, Italy.
Acerbi
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D
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D007189:Indans / Q000493:pharmacokinetics / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007189:Indans; C047759:delapril