Single and repeated dosing of the converting enzyme inhibitor perindopril to normal subjects

Abstract

The new orally active angiotensin converting enzyme (ACE) inhibitor perindopril (S9490-3) was evaluated in 18 normotensive men. In three subjects the pressor response to exogenous angiotensin I was tested. A 8 mg oral dose reduced the pressor response by greater than 80%. Single oral perindopril doses of 2, 4, 8, and 16 mg were given to groups of five subjects each. Eight and 16 mg decreased plasma ACE activity within 4 hours to less than 10% of control; 72 hours later, plasma ACE activity was still reduced by at least 40%. Doses of 4 and 8 mg po once a day were then given for 8 days to two groups of six subjects. Four hours after the first and the last morning doses, plasma angiotensin II, aldosterone, and plasma ACE activity fell significantly, whereas blood angiotensin I and plasma renin activity rose. There was no evidence of drug accumulation. No significant change in blood pressure or heart rate was observed. Thus in normotensive subjects, perindopril seems an effective, orally active, long-lasting ACE inhibitor.

Determinants of increased angiotensin II levels in severe chronic heart failure patients despite ACE inhibition

“…Active renin protein and angiotensin I levels were elevated in the patients with elevated angiotensin II levels. It has been well described that renin and angiotensin I accumulate during short-term and long-term ACE inhibition [23][24][25]. Since all our patients had been on a steady dose of ACE inhibitor for at least three months, this does not account for the different hormone levels we found in our population.…”

Chronobiology and Pharmacologic Modulation of the Renin–Angiotensin–Aldosterone System in Dogs: What Have We Learned?

“…Using a low-sodium diet (LSD) model of RAAS activation, our research shows that benazeprilat markedly influences the dynamics of the systemic RAAS following single and repeated oral administrations of benazepril at its recommended dose (0.25-1.0 mg/kg q24 h) in dogs (Mochel et al 2013b). In this study, treatment with benazepril triggered an apparent decrease in AII and ALD, together with a sustained elevation of RA, as a consequence of benazeprilat-induced interruption of the AII-renin negative feedback loop (Bussien et al 1986;Steele et al 2002). As expected, changes in ALD were followed by a significant reduction of potassium renal excretion.…”

The pharmacokinetics and pharmacodynamics of perindopril in patients with hepatic cirrhosis.

“…Perindopril is an ACE inhibitor which has been studied in young healthy subjects (Ajayi et al, 1986;Bussien et al, 1986;Lees & Reid, 1987a) and in patients with essential hypertension (Lees & Reid, 1987b). It is an ester pro-drug and has to be converted by de-esterification to its active form, perindoprilat.…”