Biomedical subjects

J P Santoni

Publications and source records attributed to J P Santoni.

At least 19 recordsLinked to original sources

PubMed2001

Mizolastine in the treatment of seasonal allergic rhinoconjunctivitis: a European clinical experience with 5408 patients managed in daily practice (PANEOS SAR Study).

BACKGROUND: Mizolastine, a potent H1 antihistamine with additional antiallergic properties, is marketed for the treatment of allergic rhinoconjunctivitis and urticaria. The objective was to investigate the safety and effectiveness of mizolastine under conditions of daily practice in patients with seasonal allergic rhinoconjunctivitis (SAR). METHODS: In an open multicenter study, mizolastine 10 mg daily was administered for 14 days during the pollen season. Nasal and ocular symptoms, time to onset of symptom relief, and effect of the drug on diurnal alertness were evaluated. Safety was evaluated on the basis of self-reported adverse events (AE). RESULTS: A total of 5408 patients (36+/-14 years of age, females=57%) with a history of SAR for 8+/-9 years were treated for a mean of 17.1+/-5.0 days. SAR symptoms improved in 93% and decreased by at least 50% in 86% of patients; 78% reported improvement after the first drug intake and 51% from the first hour. Sixty-nine percent considered mizolastine more effective than other antihistamines taken previously. The incidence of AE was low (3.8%). CONCLUSION: The high responder rate, the rapid onset of action, and the low incidence of AE observed in this large multicenter study confirm the previously reported beneficial efficacy and safety of mizolastine in the management of SAR.

Adolescent↗

PubMed2000

Diltiazem in acute myocardial infarction treated with thrombolytic agents: a randomised placebo-controlled trial. Incomplete Infarction Trial of European Research Collaborators Evaluating Prognosis post-Thrombolysis (INTERCEPT)

BACKGROUND: Diltiazem reduces non-fatal reinfarction and refractory ischaemia after non-Q-wave myocardial infarction, an acute coronary syndrome similar to the incomplete infarction that occurs after successful reperfusion. We postulated that this agent would reduce cardiac events in patients after acute myocardial infarction treated initially with thrombolytic agents-a clinical application previously unexplored with heart-rate-lowering calcium antagonists. METHODS: A prospective, randomised, double-blind, sequential trial was done in 874 patients with acute myocardial infarction, but without congestive heart failure, who first received thrombolytic agents. Patients received either 300 mg oral diltiazem once daily, or placebo, initiated within 36-96 h of infarct onset, and given for up to 6 months. The trial primary endpoint was the cumulative first event rate of cardiac death, non-fatal reinfarction, or refractory ischaemia. Additional prespecified endpoints included several composites of non-fatal cardiac events (non-fatal reinfarction combined with refractory ischaemia, all recurrent ischaemia, or the need for myocardial revascularisation). The diagnosis of ischaemia, whether refractory or recurrent, and the need for myocardial revascularisation, was always based on objective electrocardiographical evidence of ischaemia, either at rest or on exertion. RESULTS: For the trial primary endpoint, 131 events occurred in the 444 placebo patients and 97 events in the 430 diltiazem patients (hazard ratio 0.79; 95% CI, 0.61-1.02; p=0.07). For non-fatal cardiac events, diltiazem treatment was associated with a relative decrease (0.76; 0.58-1.00) in the combined event rate of non-fatal reinfarction and refractory ischaemia. There was a similar decrease in the composite non-fatal endpoints of non-fatal reinfarction combined with all recurrent ischaemia (0.80; 0.64-1.00) and non-fatal reinfarction combined with the need for myocardial revascularisation (0.67; 0.46-0.96). The need for myocardial revascularisation alone was significantly reduced by 42% (0.61; 0.39-0.96). No major safety issues were encountered. CONCLUSIONS: Diltiazem did not reduce the cumulative occurrence of cardiac death, non-fatal reinfarction, or refractory ischaemia during a 6-month follow-up, but did reduce all composite endpoints of non-fatal cardiac events, especially the need for myocardial revascularisation.

Calcium Channel Blockers↗

PubMed1997

Clinical uroselectivity: evidence from patients treated with slow-release alfuzosin for symptomatic benign prostatic obstruction.

OBJECTIVE: To assess the safety profile of slow-release (SR) alfuzosin in the treatment of benign prostatic obstruction (BPO), with special attention to orthostatic blood pressure changes, postural symptoms and efficacy. PATIENTS AND METHODS: Two placebo-controlled studies involving 588 patients (292 receiving SR alfuzosin 5 mg twice daily and 296 a placebo) were pooled; 51% of the patients were > or = 65 years of age and 43% had associated cardiovascular disease including hypertension and/or were receiving concomitant antihypertensive drugs. RESULTS: SR alfuzosin was very well tolerated with an overall incidence of adverse events similar to that of placebo (18.5% and 15.8% of patients, respectively) and an overall incidence of withdrawal from therapy for adverse events lower than that of placebo (3.4% and 5.7%, respectively). Adverse events potentially related to vasodilatation were infrequent with SR alfuzosin (the same incidence as with placebo, i.e. 2.7% of patients) and these adverse events occurred mainly during the first month of alfuzosin treatment. The effect on supine blood pressure was minimal. In the subgroups of elderly and hypertensive patients treated with SR alfuzosin, the cumulative incidence of asymptomatic orthostatic hypotension during the first month of treatment was slightly higher than with placebo with no objective consequences on the incidence of adverse events. The clinical efficacy of SR alfuzosin was confirmed by a significant improvement in urinary symptoms and a significant increase in maximum flow rates. CONCLUSION: SR alfuzosin (10 mg/day) can be administered safely without titration in patients with BPO, even in elderly and hypertensive patients. Its favourable benefit/risk ratio allows alfuzosin to be classified as a clinically uroselective alpha 1-blocker. Specific analysis of orthostatic changes in blood pressure is important when assessing the safety profile of an alpha 1-blocker in patients with BPO.

Adrenergic alpha-Antagonists↗

PubMed1995

Design of a placebo-controlled clinical trial of long-acting diltiazem and aspirin versus aspirin alone in patients receiving thrombolysis with a first acute myocardial infarction. Incomplete Infarction Trial of European Research Collaborators Evaluating Prognosis Post-Thrombolysis (diltiazem) (INTERCEPT) Research Group.

Several pharmacologic forms of adjunctive therapy, designed to enhance the efficacy of thrombolysis following acute myocardial infarction (AMI), are being explored. However, few studies have assessed the use of standard secondary prevention therapies (beta-blockers, angiotensin-converting enzyme inhibitors, magnesium, calcium antagonists, etc.) for antecedent thrombolysis. Although calcium antagonists have not been shown to alter post-AMI mortality, diltiazem has been shown to reduce recurrent nonfatal infarction and myocardial ischemia following non-Q-wave AMI. Because both non-Q-wave AMI and AMI treated with thrombolytic therapy result in early reperfusion and clinical manifestations of "incomplete infarction" (i.e., aborted transmural infarction), we hypothesize that prophylactic administration of diltiazem to AMI patients who receive thrombolysis before other therapies might decrease ischemic complications. We have initiated a multicenter, randomized, placebo-controlled, double-blind, parallel-group comparison of long-acting diltiazem 300 mg/day and aspirin 160 mg/day versus aspirin 160 mg/day alone in up to 920 patients with an uncomplicated first AMI (no heart failure or left ventricular dysfunction) within 36 to 96 hours of receiving thrombolysis. Active enrollment is under way at 46 centers in the United Kingdom, Belgium, The Netherlands, and Denmark. This trial (known as the Incomplete INfarction Trial of European Research Collaborators Evaluating Prognosis Post-Thrombolysis [diltiazem], or INTERCEPT) represents the first long-term, large-scale, prospective study of a calcium antagonist administered post-thrombolysis as adjunctive therapy to AMI patients in which the primary trial objective is to assess the effect of blinded therapy on the 6-month cumulative occurrence of a combined clinical end point (cardiac death, recurrent nonfatal AMI, and medically refractory ischemia).

Adolescent↗

PubMed1994

Belgian multicenter clinical study of alfuzosin, a selective alpha 1-blocker, in the treatment of benign prostatic hyperplasia. The Alfuzosin Belgian Group.

The effects of alfuzosin, a potent alpha 1-blocker, were assessed in patients with benign prostatic hyperplasia, in a double-blind, multicenter, placebo-controlled, cross-over study. Treatment duration was 4 weeks for both alfuzosin and placebo. A significant beneficial effect of alfuzosin (7.5 to 10 mg a day) on clinical subjective and objective criteria was observed as compared to placebo: total Boyarsky score decreased by 1.63 points, peak urinary flow improved by 2.03 ml/sec. Alfuzosin was well tolerated, the observed adverse events corresponded to the pharmacological properties of this compound, and resolved rapidly.

Adrenergic alpha-Antagonists↗

PubMed1991

A double-blind comparison of perindopril and hydrochlorothiazide-amiloride in mild to moderate essential hypertension.

The aim of this 3-month double-blind multicenter trial was to compare the antihypertensive efficacy and tolerability of the ACE inhibitor perindopril with those of a diuretic combination. After 1 month of receiving placebo, 165 patients with essential hypertension were randomised to perindopril 4 mg (n = 82) or to 50 mg hydrochlorothiazide + 5 mg amiloride (n = 83). The patients were treated for 3 months with monthly assessments, "uncontrolled" patients (DBP greater than 90 mm Hg) had their dosage doubled and then, if necessary, atenolol 50 mg was added. At the end of the 3-month study, mean decreases in supine and standing systolic and diastolic blood pressures were similar in both groups. In the perindopril group, BP control was obtained in 56% of the patients with the 4 mg dosage and required an increase to 8 mg alone in 16% and with atenolol in 5%. The corresponding percentages in the diuretic group were 48, 23 and 13%. The overall percentage of "controlled" patients was similar in the 2 groups, respectively 78 and 84%. The nature and incidence of complaints were comparable in the 2 groups. Adverse laboratory changes were more frequent in the diuretic group: decrease in blood sodium (140.5 vs 139.1 mmol/l; P less than 0.01), potassium (4.2 vs 3.9 mmol/l; P less than 0.01) with 10 patients having significant hypokalemia, increase in blood urea, triglycerides and uric acid. By contrast, a transient increase in blood potassium with a decrease in triglycerides was observed in the perindopril group.

Adolescent↗

PubMed1990

The effect of perindopril and hydrochlorothiazide alone and in combination on blood pressure and on the renin-angiotensin system in hypertensive subjects.

The pharmacodynamic effects and acceptability of perindopril (4 mg daily) and hydrochlorothiazide (25 mg daily) given alone or in combination for 1 month were investigated in a double-blind, placebo controlled, parallel group study. The pharmacokinetics of perindopril and its active metabolite perindoprilat and the time course of angiotensin converting enzyme inhibition were studied for 72 h following the last dose of treatment in the two appropriate groups. Similar decreases in blood pressure were seen 24 h after the last dose of perindopril or hydrochlorothiazide (11/7 mm Hg supine) given alone at these doses. The effect of these drugs given together was additive on diastolic blood pressure and synergistic on systolic blood pressure (24.5/12.6 mm Hg supine) taking into account the placebo response. The significant increase in plasma renin activity produced by perindopril alone was potentiated by concurrent administration of hydrochlorothiazide. The formation of perindoprilat was slightly reduced in the group also receiving hydrochlorothiazide and there was a very small reduction in ACE inhibition in this group. Perindopril, whether given alone or in combination with hydrochlorothiazide, was well tolerated and produced no clinically significant change in routine haematology or serum biochemistry. The additive or synergistic effects of perindopril and hydrochlorothiazide on blood pressure must be due to their complementary physiological actions and not to a pharmacokinetic interaction.

Adult↗

PubMed1990

Vascular effects of intravenous infusion of the angiotensin converting enzyme inhibitor perindoprilat.

This study was aimed at evaluating the hemodynamic changes after acute inhibition of the renin-angiotensin system in hypertensive patients. Twenty-one subjects with essential hypertension were randomized into three groups of seven subjects each. In group I, the direct vascular vasodilator dihydralazine was administered at a dose of 4 micrograms/kg per min. Groups II and III received a continuous intravenous infusion of the angiotensin converting enzyme (ACE) inhibitor perindoprilat at a dose of 1 microgram/kg per min and 2.5 micrograms/kg per min, respectively. Brachial artery hemodynamics and aortic distensibility were evaluated non-invasively. Vascular reactivity was evaluated by the cold-pressor test. In all three groups, an identical decrease in blood pressure was observed (P less than 0.001), followed by a slight (but not significant) decrease in the heart rate in both perindoprilat groups, and an important tachycardia in the dihydralazine group (P less than 0.001). Brachial artery diameter was increased in the high-dose perindoprilate group from 0.437 +/- 0.014 to 0.479 +/- 0.013 cm (P less than 0.02), but remained unchanged in the two other groups. No significant changes in brachial artery mean blood velocity and blood flow were observed. In group III, aortic distensibility increased almost twice as much as in the two other groups, but this difference was not statistically significant. The pressor response to the cold-pressor test was not modified in the three groups; the heart rate response was almost completely abolished in groups II and III, but increased in the dihydralazine group (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Systemic and regional hemodynamic interactions of perindopril and nitrendipine in the spontaneously hypertensive rat.

Adult spontaneously hypertensive rats (SHR) were daily treated for 2 weeks with perindopril [an angiotensin-converting enzyme (ACE) inhibitor] and nitrendipine (a calcium antagonist) alone or in combination. Blood pressure (BP), heart rate (HR), and diuresis were assessed weekly in conscious rats, and systemic and regional hemodynamics were investigated by the microsphere technique at the end of the treatment in anesthetized rats. Both perindopril (2 mg.kg-1.d-1) and nitrendipine (10 mg.kg-1.d-1) decreased BP to the same extent, but perindopril exerted a longer action. The hemodynamic profile of each drug was respectively consistent with the classic ones of ACE inhibitors and calcium antagonists already described in the literature. With combination of the two treatments, effects were at least additive, except that the nitrendipine-induced tachycardia was partially reduced by perindopril. BP reduction was additive, and significant potentiation was shown at the systemic [cardiac index (CI) increase, total peripheral resistance (TPR) decrease] and some regional (hepatic, muscular, and cutaneous vasodilations) levels. These results, which are in agreement with the different mechanisms of action of the two drugs, emphasize the advantage of combining perindopril with nitrendipine for treatment of hypertension.

Animals↗

PubMed1990

[Long-term decrease of microalbuminuria after one year of treatment with perindopril in hypertensive diabetic patients].

We studied the effects of perindopril, an angiotensin converting enzyme (ACE) inhibitor administered during 12 months, on creatinine clearance, albuminuria and glycaemic control in diabetic subjects with mild to moderate hypertension. After 1 month placebo, 40 insulin-treated patients were divided into 3 groups based upon their urinary albumin excretion rate. Group 1 had a normoalbuminuria (less than 15 mg/24 h), group II had a microalbuminuria (15-150 mg/24 h) and group III had a macroproteinuria (greater than 150 mg/24 h and Albustix +). They were given perindopril 4 to 8 mg orally once daily, and received a stable diet. Diastolic blood pressure was normalized within the first 3 months in 80% of the patients. From these, 28 (14.7 and 7 from groups I, II and III respectively) were followed during a total active treatment period of 12 months. They were matched for age, duration of diabetes and hypertension, systolic and diastolic blood pressures, daily insulin dose, postprandial plasma C-peptide and quality of glycaemic control. Mean supine diastolic blood pressure was decreased by 15 and 18% at 1 and 12 months respectively. Heart rate was not significantly modified. At 3 months, plasma ACE activity was nearly totally inhibited while plasma renin activity was markedly increased. In patients of group II, microalbuminuria was reduced from 66 +/- 13 (mean +/- SEM after placebo) to 39 +/- 6 mg/24 h after 1 month perindopril and this effect was maintained at 12 months. In group I, albuminuria remained within the normal range. In group III, macroproteinuria was not consistently modified by perindopril. Creatinine clearance did not change and glycaemic control remained stable throughout the study in the 3 groups. No major side effects were observed. We conclude that perindopril normalizes blood pressure in a large majority of hypertensive diabetic patients without affecting the quality of diabetes control. It also induces a marked and sustained reduction of microalbuminuria in patients at risk of developing diabetic nephropathy.

Adult↗

PubMed1990

A double blind comparison of perindopril and atenolol in essential hypertension.

A multicentre randomised double-blind trial was performed in order to compare the therapeutic efficacy and acceptability of the angiotensin converting enzyme (ACE) inhibitor perindopril with those of atenolol in mild to moderate hypertension. After one month of placebo, 173 patients with supine diastolic blood pressure (DBP) between 95 and 125 mmHg were randomised to receive perindopril 4 mg once daily or atenolol 50 mg once daily. Monthly assessments were made for three months. Treatment was adjusted at these visits if supine DBP was greater than 90 mmHg; the dose was first doubled (8 mg perindopril or 100 mg atenolol once daily) and then hydrochlorothiazide was added. The pretreatment blood pressure levels were similar in both groups. Supine DBP was 105.5 +/- 0.9 mmHg (n = 85) in the perindopril group and 106.9 +/- 0.9 mmHg (n = 88) in the atenolol group. At the end of the third month, the study target blood pressure (supine DBP less than or equal to 90 mmHg) was achieved in a significantly (P = 0.006) larger percentage of patients in the perindopril group (78%) than in the atenolol group (58%). This appeared to be due to a greater potentiation of the antihypertensive effect by the addition of diuretic to perindopril than to atenolol. The fall in systolic blood pressure was significantly greater in the perindopril group than in the atenolol group (supine: 26.5 +/- 2.0 mmHg vs. 20.6 +/- 2.0 mmHg; P = 0.042) although the fall in DBP was comparable (supine: perindopril 17.4 +/- 0.9 mmHg, atenolol 15.6 +/- 1.1 mmHg; P = 0.195).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1989

[First intention treatment of arterial hypertension. Effectiveness and safety of perindopril].

Inhibitors of the angiotensin conversion enzyme (ICE) represent an effective and well tolerated therapeutic class, for the treatment of arterial hypertension. The antihypertensive efficacy or perindopril, an ICE active in one single daily dose, is at least equal to that of reference antihypertensive drugs administered at usual doses. The possibility of occurrence of some side-effects while using ICE, has resulted in a particular attention in evaluating the safety of perindopril. First, the renal function was monitored. During essential hypertension, no significant variation of the creatininemia was observed with long-term administration of the drug (12 months). In elderly hypertensive patients or patients with chronic renal insufficiency, the glomerular filtration is also preserved, except during rare occurrences of decreased creatinine clearance, especially after adjunction of hydrochlorothiazide. A discrete elevation of the kaliemia without clinical significance is observed when perindopril is used as a single drug. Reports of symptomatic hypotension with perindopril are rare (0.2%), even in situations of water and sodium depletion. Among other side-effects of ICE, cough, more recent, was thoroughly investigated. Its frequency was determined during a double blind trial comparing perindopril (1.2%) with captopril (2.4%). It was also evaluated during a long-term study concerning 632 hypertensive patients (391 patients treated in 1 year); its incidence is the 2.9 p. cent and it resulted in discontinuation of the treatment in 8 cases. In this study, 36 patients interrupted the treatment prematurily because of an adverse reaction (5.7%). Finally no harmful drug interaction was reported. The favorable tolerance profile of perindopril is combined with a beneficial effect on the functional and structural modifications of the heart and large vessels related to hypertension.

Antihypertensive Agents↗

PubMed1989

[Ambulatory registration of arterial pressure during treatment with perindopril. Effects on systolic pressure and hemodynamic implications].

The effects of perindopril on the 24-hour arterial pressure levels were evaluated by ambulatory recording in 21 patients (mean age 48 +/- 2 years) with mild to moderate hypertension. At the end of a 3 months treatment with perindopril (4 to 8 mg per day in one dose), comparison by variance analysis of the mean values of arterial pressure over 24 hours before and after treatment showed a significant decrease of SAP (from 144 +/- 3 to 133 +/- 3 mmHg, p less than 0.01) and DAP (from 95 +/- 2 to 87 +/- 2 mmHg, p less than 0.01). The fall in arterial pressures was more pronounced during day-time (7 a.m. to 10 p.m.) than at night. Particular attention was paid to the reduction of systolic pressure owing to its relation with arterial compliance. There was a significant correlation between ambulatory recordings of SAP and DAP before and after treatment (r = 0.82 and 0.76 respectively, p less than 0.001). Calculation and comparison of the corresponding regression slope showed that for any given level of DAP, SAP was lower after than before treatment. This effect is related to the increase of arterial compliance observed after treatment with perindopril, as already reported by other authors.

Antihypertensive Agents↗

PubMed1989

[Significance of inhibitors of conversion enzymes in elderly subjects. The example of perindopril].

The effectiveness and safety of perindopril in elderly hypertensive patients has clearly been demonstrated. In a randomized, double-blind drug versus placebo study involving 34 such patients of mean age 84 years, we observed a 10 p. 100 fall in systolic arterial pressure (p less than 0.01) and a 9 p. 100 fall in diastolic arterial pressure (p less than 0.01) in the perindopril group. The corresponding figures in the placebo group were 5 p. 100 and 4 p. 100 respectively, the difference between the two groups not being significant. The drug was well tolerated, both clinically and biochemically. However, a significant (p less than 0.01) increase in blood potassium level (albeit within normal limits) was observed in the treated group. An open trial conducted in 91 patients (mean age 79.1 years) followed up for 6 years confirmed the acceptability of the drug despite a transient decrease of creatinine clearance recorded in one patient. The effectiveness of perindopril, evaluated less unquestionably in this open trial, was excellent, the hypertension being controlled at the end of treatment in 92.5 p. 100 of the patients. In a trial performed on healthy volunteers, Reid found that perindopril had a greater effect of arterial pressure in elderly subjects, probably due in part to their high blood pressure and to an earlier and more prolonged inhibition of the angiotensin-converting enzyme (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMed1989

[Tolerance and safety of the use of perindopril].

Angiotensin-converting enzyme inhibitors (ACEI) constitute an effective and well tolerated class of drugs for the treatment of arterial hypertension. Yet they have been blamed for the occurrence of side-effects the most frequently reported of which are renal function impairment, hypotension and cough. For this reason, the renal function of hypertensive patients has been evaluated after short - and long - term treatment with perindopril. In patients with normal renal function on short-term treatment (1 and 5 days) perindopril produced an increase of renal plasma flow without change in glomerular filtration. In long-term treatment (up to 18 months), no significant change in plasma creatinine level was observed. In old age hypertensive patients or in patients with chronic renal failure glomerular filtration was also preserved, apart from rare cases of creatinine clearance reduction, notably after addition of hydrochlorothiazide. A very slight and clinically not significant rise of kaliemia was noted when perindopril was used as single-drug treatment. Cases of symptomatic hypotension were rare (0.2 p. 100), even in situations of water and salt depletion. Among the other side-effects of ACEI, cough, which has more recently been described, has carefully been looked for. Its incidence has been determined in a double-blind trial comparing perindopril (1.2 p. 100) with captopril (2.4 p. 100). It has also been evaluated in a long-term study involving 632 hypertensive patients, 391 of whom were treated for 1 year; its incidence then was 2.9 p. 100, and drug withdrawal was required in 8 cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1989

Experience with perindopril in normal volunteers.

The new orally active angiotensin converting enzyme (ACE) inhibitor perindopril was evaluated in normotensive men. Doses of 2 to 16 mg were given once a day for up to one week. Single oral doses of perindopril were found to blunt the pressor response to exogenous angiotensin I in a dose-dependent manner. The drug-induced ACE inhibition, as estimated by the measurement of plasma ACE activity, was maximal 4 to 8 hours post drug intake. ACE activity was still importantly reduced 24 hours after dosing. Plasma levels of angiotensin II and aldosterone decreased significantly whereas plasma renin activity and blood angiotensin I levels rose during peak ACE inhibition induced by the 4 and 8 mg doses. However, circulating levels of angiotensin II returned to baseline 24 hours after dosing, both on the first day of treatment and after one week of administration. ACE inhibition with perindopril did not affect blood pressure and heart rate in any consistent manner. There was no evidence for drug accumulation during repeated administration. The novel ACE inhibitor was well tolerated and produced no change in routine laboratory tests. The long-acting ACE inhibitor perindopril appears therefore to be effective when given orally in a dose range of 4 to 16 mg.

Angiotensin I↗

PubMed1989

Experience with perindopril in normal volunteers.

The new orally active angiotensin converting enzyme (ACE) inhibitor perindopril was evaluated in normotensive men. Doses of 2 to 16 mg were given once a day for up to one week. Single oral doses of perindopril were found to blunt the pressor response to exogenous angiotensin I in a dose-dependent manner. The drug-induced ACE inhibition, as estimated by the measurement of plasma ACE activity, was maximal 4 to 8 hours post drug intake. ACE activity was still markedly reduced 24 hours after dosing. Plasma levels of angiotensin II and aldosterone decreased significantly, whereas plasma renin activity and blood angiotensin I levels rose during peak ACE inhibition induced by the 4 and 8 mg doses. However, circulating levels of angiotensin II returned to baseline values 24 hours after dosing, both on the first day of treatment and after one week of administration. ACE inhibition with perindopril did not consistently affect blood pressure and heart rate. There was no evidence for drug accumulation during repeated administration. The novel ACE inhibitor was well tolerated and produced no change in routine laboratory tests. The long-acting ACE inhibitor perindopril therefore appears to be effective when given orally in a dose range of 4 to 16 mg.

Acetylcholinesterase↗

PubMed1989

Captopril versus perindopril: a double blind study in essential hypertension.

This was a double blind, parallel group, multicentre comparison of the therapeutic efficacy and acceptability of perindopril and captopril in essential hypertension. After one month of placebo, 165 patients with supine diastolic blood pressure (DBP) between 95 and 125 mmHg were randomised to perindopril 4 mg once daily or captopril 25 mg twice daily orally. The perindopril group (n = 82) had significantly higher pretreatment DBP (105.4 +/- 0.8 mmHg vs 102.3 +/- 0.6 mmHg) but other demographic variables were similar. Assessment was monthly for three months: 'uncontrolled' patients (DBP greater than 90 mmHg) had the dose doubled and then hydrochlorothiazide added. Two of the six withdrawals were attributed to drug side effects and were in the captopril group. There was no significant difference in the number of withdrawals or incidence of side effects between the drugs. The final titrated treatments were similar and monotherapy normalised DBP in 49% of each group. The final 'control' rate was higher with perindopril than captopril: 75% vs 57%, P = 0.016. The overall fall in DBP was greater in the perindopril group: 26.5 +/- 1.9 mmHg vs 18.9 +/- 1.9 mmHg, P = 0.005. The doses of diuretic were similar in the two groups. The DBP of patients who received only monotherapy for three months also fell more in the perindopril group (-17.5 +/- 1.4 mmHg vs -13.9 +/- 1.0 mmHg, P less than 0.01). At the doses studied, perindopril was more effective than captopril in lowering DBP, either as monotherapy or in combination with a diuretic.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗