Evaluation of the dose-effect relationship of a new ace inhibitor (perindopril) by an automatic blood pressure recorder

Luccioni, R; Francès, Y.; Gass, Ricardo; Schwab, C. William; Santoni, J P; Perret, Laurent

doi:10.1093/oxfordjournals.eurheartj.a062410

Cited by 19 publications

(10 citation statements)

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“…1984;Heel et a1. 1979;Luccioni et al 1988) and is consistent with the results of Weinberger (1982) showing the synergistic antihypertensive effect of the combination ACE inhibitor/diuretic. As expected, there was a significant decrease in mean heart rate with atenolo1.…”

Section: Discussionsupporting

confidence: 88%

“…In healthy subjects, orally administered perindopril 1 to 16mg has been shown to cause dose-dependent ORIGINAL RESEARCH ARTICLE inhibition of plasma ACE activity with the maximal effect occurring at 4 to 6 hours, and persisting ACE inhibition 24 hours after administration of 4 or 8mg (Bussien et al 1986;Lees & Reid 1987a). Previous dose-response studies have shown perindopril to have antihypertensive activity at doses of ~ 4mg once daily (Lees & Reid 1987b;Luccioni et al 1988).…”

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confidence: 99%

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Antihypertensive Effect and Acceptability of Perindopril

et al. 1991

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The aim of this 3-month double-blind study was to assess the antihypertensive effect and acceptability of perindopril in comparison with atenolol in patients with mild to moderate essential hypertension. After a 4-week run-in placebo period, 40 patients with supine diastolic blood pressure (DBP) between 95 and 120mm Hg were randomised to receive perindopril 4mg or atenolol 50mg once daily. If supine DBP was> 90mm Hg, treatment was adjusted monthly: first by doubling the dose and then by the addition of chlorthalidone 50mg. Except for standing DBP, which was higher in the perindopril group than in the atenolol group, the 2 groups were homogeneous prior to treatment. After 3 months of active treatment, the decrease in supine blood pressure and standing DBP was not significantly different between the 2 groups. In contrast, the fall in standing systolic blood pressure was greater with perindopril than with atenolol. The percentage of patients (85%) who achieved supine DBP of ~ 90mm Hg in the perindopril group was not significantly different from the atenolol group (80%). Monotherapy resulted in control of supine DBP in 55% of the perindopril group and 65% of the atenolol group; the addition of chlorthalidone resulted in control of supine DBP in 30 and 15%, respectively. No patient was withdrawn from the study. The nature and incidence of side effects were similar between the 2 groups. Changes in laboratory parameters were minor and not significantly different between the 2 groups.Perindopril was as effective as atenolol in lowering blood pressure. Clinical and biological acceptability was satisfactory and similar with both drugs. Perindopril may therefore be recommended as first-line treatment for mild to moderate essential hypertension.

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Section: Discussionsupporting

confidence: 88%

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confidence: 99%

Antihypertensive Effect and Acceptability of Perindopril

et al. 1991

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“…This to the active diacid metabolite perindoprilat (S 9780) long terminal phase seems to reflect the high affinity of (Laubie et al, 1984). Minor metabolic pathways lead to perindoprilat for plasma ACE and can be considered to glucuronide-conjugates (S 9490 glucuronide and S 9780 be relevant to its pharmacodynamics (Devissaguet et al, tension and of congestive heart failure (Luccioni et al, 1988;Thuillez et al, 1987). Since renal failure is often associated with these conditions and since the kidney is the main route of elimination of perindoprilat, this study was designed to investigate the influence of various degrees of renal insufficiency on the pharmacokinetics of perindopril and its main metabolites after a single oral dose.…”

Section: Introductionmentioning

confidence: 99%

Single dose pharmacokinetics of perindopril and its metabolites in hypertensive patients with various degrees of renal insufficiency.

Verpooten

Génissel

Thomas

et al. 1991

Brit J Clinical Pharma

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1 Perindopril is a prodrug which is hydrolysed in vivo to the active metabolite perindoprilat, an angiotensin‐converting enzyme inhibitor. Perindoprilat glucuronide is also found in plasma. 2 The pharmacokinetics of perindopril and its metabolites were studied after administration of a single 4 mg dose to hypertensive patients with various degrees of renal failure. 3 The absorption and elimination of perindopril were not influenced by the degree of renal failure. 4 The mean area under the serum concentration‐time curve of the active metabolite perindoprilat increased from 93 ng ml‐1 h in subjects with normal renal function to 1106 ng ml‐1 in patients with severe renal failure, whereas its half‐life varied from 5.0 to 27.4 h. 5 In the same subjects, the mean area under the curve of perindoprilat glucuronide increased from 78 to 513 ng ml‐1 h, while its half‐life varied from 1.8 h to 7.7 h. 6 Perindopril, perindoprilat, and perindoprilat glucuronide were dialysable. 7 The extent and duration of serum angiotensin‐ converting enzyme inhibition was augmented in renal failure. The mean area under the inhibition time curve (extrapolated to infinity) increased from 2490%.h in subjects with normal renal function to 42241 %.h in patients with severe renal impairment. The half‐life of inhibition varied from 12.1 h to 100.4 h. This effect of renal failure on the pharmacodynamics of perindoprilat was more pronounced than its influence on perindoprilat kinetics. 8 In view of the important influence of renal impairment on the elimination and action of the active substance perindoprilat, a dosage reduction of perindopril is proposed in in patients with renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…They were included if at least 75% of diastolic blood pressure recordings, made over an 8 h diurnal period using an automatic blood pressure recorder, were greater than 95 mmHg on placebo. Treatment was significantly associated with a greater reduction of blood pressure with 4 and 8 mg/day doses compared with placebo and the 2 mg/day dose [36].…”

Section: Phase II Studies: Blood Pressure Studiesmentioning

confidence: 90%

Perindopril: Beyond Lowering Blood Pressure

Zaiem

Zannad

2008

Future Cardiol.

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Perindopril, a prodrug ester of perindoprilat, is an angiotensin-converting enzyme inhibitor that lowers angiotensin II and potentiates bradykinin. This agent has proven efficacy in a wide range of cardiovascular diseases. Its efficacy, safety and tolerability are well established in the treatment of hypertension. Beyond pharmacodynamic effects shown in lowering blood pressure, perindopril was also involved in the improvement of endothelial function and the normalization of vascular and cardiac structure and function. Large morbidity-mortality trials, such as the European Trial on Reduction of Cardiac Events with Perindopril in Patients with Stable Coronary Artery Disease (EUROPA), Perindopril Protection Against Recurrent Stroke Study (PROGRESS) and Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA), have shown that treatment with perindopril reduces and prevents cardiovascular disease in a large range of patients with vascular diseases (including stable coronary disease), whether or not they are hypertensive.

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Evaluation of the dose-effect relationship of a new ace inhibitor (perindopril) by an automatic blood pressure recorder

Cited by 19 publications

References 0 publications

Antihypertensive Effect and Acceptability of Perindopril

Antihypertensive Effect and Acceptability of Perindopril

Single dose pharmacokinetics of perindopril and its metabolites in hypertensive patients with various degrees of renal insufficiency.

Perindopril: Beyond Lowering Blood Pressure

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