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At least 19 recordsLinked to original sources
PubMed1994

Quinapril and hydrochlorothiazide combination for control of hypertension: assessment by factorial design. Quinapril Investigator Group.

A factorial design method was applied in this multicentre trial of the angiotensin-converting enzyme inhibitor quinapril hydrochloride (Accupril) in combination with the diuretic hydrochlorothiazide (HCTZ) to assess the additive effects of the combination versus monotherapy, to characterise the dose-response relationship of each drug in the presence of the other and to determine if quinapril would attenuate the hypokalemic effect of HCTZ. Following a two to four week placebo-baseline period, 460 qualifying patients with a DBP > or = 100 mmHg and < or = 115 mmHg were randomised to an eight week double-blind phase with one of 16 parallel treatments: placebo, one of three doses of quinapril monotherapy, one of three doses of HCTZ monotherapy or one of nine possible corresponding combinations of quinapril and HCTZ. Mean reductions in sitting SBP/DBP at trough with combination therapy ranged from 7.8 mmHg/7.2 mmHg to 19.6 mmHg/15.1 mmHg (n = 458). Results of the response surface analyses indicate that the effects of the two drugs were additive and that the maximum antihypertensive effect of quinapril in combination with HCTZ within the doses studied is achieved approximately at a dose of 26 mg quinapril and 25 mg HCTZ. The degree of attenuation of the hypokalemic effect of HCTZ was directly related to the dose of quinapril. At 40 mg quinapril, the HCTZ dose-related decreases of serum potassium were not apparent and overall hypokalemic effects were attenuated by quinapril. Thus, the combination of quinapril and HCTZ given once daily provided additive antihypertensive effects of predictable degrees and the addition of quinapril attenuated the hypokalemic effect of HCTZ.

Adult↗
PubMed1993

Clinical consequences of angiotensin-converting enzyme inhibitor withdrawal in chronic heart failure: a double-blind, placebo-controlled study of quinapril. The Quinapril Heart Failure Trial Investigators.

OBJECTIVES: This study was performed to assess the efficacy, safety and clinical consequences of abrupt cessation of quinapril therapy in a placebo-controlled, randomized, double-blind withdrawal trial. BACKGROUND: Angiotensin-converting enzyme inhibitor therapy has assumed a pivotal role in the treatment of chronic heart failure. Quinapril hydrochloride, a nonsulfydryl angiotensin-converting enzyme inhibitor, has shown beneficial clinical effects in previous studies. METHODS: After > or = 10 weeks of single-blind quinapril therapy, 224 patients with New York Heart Association class II or III heart failure were randomized in double-blind fashion to continue quinapril (n = 114) or to receive placebo (n = 110) for 16 weeks. Changes in treadmill exercise time, New York Heart Association functional class, quality of life and symptoms of heart failure were assessed. RESULTS: Patients withdrawn to placebo had a significant deterioration in exercise tolerance (median change -16 s with placebo vs. +3 s with quinapril, p = 0.015). New York Heart Association functional class (p = 0.004) and quality of life were improved and signs and symptoms of congestive heart failure were lessened in those remaining on quinapril therapy compared with those receiving placebo. During double-blind treatment, 18 patients were withdrawn from the placebo group because of worsening heart failure compared with 5 patients withdrawn from quinapril treatment (p < 0.001). Rather than a precipitous deterioration of clinical status or early incidence of adverse events, withdrawal from quinapril was associated with steady worsening of heart failure, beginning 4 to 6 weeks after randomization to placebo. CONCLUSIONS: Quinapril is effective and safe for maintaining clinical stability in patients with moderate congestive heart failure. Withdrawal of quinapril from patients with heart failure results in a slow progressive decline in clinical status.

Aged↗
PubMed1998

Comparison of effects of quinapril and metoprolol on glycaemic control, serum lipids, blood pressure, albuminuria and quality of life in non-insulin-dependent diabetes mellitus patients with hypertension. Swedish Quinapril Group.

OBJECTIVE: To compare the long-term effects of the angiotensin-converting enzyme (ACE)-inhibitor quinapril and the cardioselective beta-adrenergic blocking agent metoprolol on glycaemic control, with glycosylated haemoglobin (HbA1c) as the principal variable, in non-insulin-dependent diabetes mellitus (NIDDM) patients with hypertension. DESIGN: A randomized, double-blind, double-dummy, multicentre study during 6 months preceded by a 4 week wash-out and a 3 week run-in placebo period. Quinapril (20 mg) and metoprolol (100 mg, conventional tablets) were given once daily. No change was made in the treatment of diabetes (diet and hypoglycaemic agents). SUBJECTS: Seventy-two patients fulfilling the criteria were randomized and entered the double-blind period. Twelve patients did not complete the study. Sixty patients, 26 on quinapril and 34 on metoprolol, were available for the final analysis. MAIN OUTCOME MEASURES: The effect was assessed by changes in HbA1c, the fasting serum glucose and the post-load serum glucose, C-peptide and insulin levels during the oral glucose tolerance test. RESULTS: In the quinapril group, the fasting serum glucose, oral glucose tolerance and the C-peptide and insulin responses, determined as the incremental area under the curves (AUC), showed no change, but the mean HbA1c level increased from 6.2 +/- 1.1% to 6.5 +/- 1.3% (P < 0.05). In the metoprolol group, the rise in the mean level of HbA1c, from 6.3 +/- 1.0% to 6.8 +/- 1.3% (P < 0.01), tended to be more marked than after quinapril, although there was no significant difference between the increments. The mean fasting serum glucose showed an increase from 9.1 +/- 1.9 mM to 10.1 +/- 2.8 mM (P < 0.01) which correlated significantly with the duration of diabetes (P < 0.01) and the increase in fasting serum triglycerides (P < 0.001). Moreover, in the metoprolol group we found significant decreases in the oral glucose tolerance as well as C-peptide and insulin responses to the glucose load. CONCLUSIONS: Treatment with quinapril for 6 months appears to have advantages over metoprolol in NIDDM patients with hypertension. Although treatment with quinapril or metoprolol over 6 months was concomitant with a rise in the HbA1c, increased fasting blood glucose, decreased oral glucose tolerance and decreased C-peptide and insulin responses to a glucose challenge were observed only in patients treated with metoprolol.

Adrenergic beta-Antagonists↗
PubMed2001

Effects of quinapril on clinical outcome after coronary artery bypass grafting (The QUO VADIS Study). QUinapril on Vascular Ace and Determinants of Ischemia.

The QUO VADIS study was designed to explore whether 1 year of angiotensin-converting enzyme inhibition with quinapril (40 mg/day) would decrease ischemia in patients who underwent coronary artery bypass grafting (CABG). Patients (n = 149) scheduled for CABG were randomized 4 weeks before surgery. Study medication was used from randomization up to 1 year after CABG. Exercise testing was performed at randomization; the exercise test was repeated 1 year after CABG and patients underwent 48-hour Holter monitoring. Clinical ischemic events were recorded and defined as death, revascularization, myocardial infarction, recurrence of angina pectoris, ischemic stroke, or transient ischemic attack. Baseline characteristics were similar between groups. Total exercise time increased overall by 75 +/- 76 seconds 1 year after CABG (placebo +79 +/- 75 seconds, quinapril +72 +/- 79 seconds, p = 0.6). All patients had ischemic ST-segment changes at randomization; 33% of patients had ischemic ST-segment changes 1 year after CABG (placebo 29%, quinapril 37%, p = 0.4). On Holter monitoring, the number of patients experiencing > or = 1 episodes of ischemia was equal in both groups. Treatment with quinapril significantly reduced clinical ischemic events after CABG: 15% in patients on placebo versus 4% of patients on quinapril (hazard ratio 0.23, 95% confidence interval 0.06 to 0.87, p = 0.02). Long-term quinapril treatment significantly reduced clinical ischemic events within 1 year after CABG, although ischemia at exercise testing and Holter monitoring was unchanged.

Aftercare↗
PubMed1994

Quinapril. A reappraisal of its pharmacology and therapeutic efficacy in cardiovascular disorders.

Following systemic absorption, quinapril is converted by de-esterification to quinaprilat (the active diacid metabolite), an inhibitor of angiotensin converting enzyme (ACE). Pharmacodynamic studies in animals indicate inhibition of ACE both in plasma and at tissue sites, such as the arterial wall and heart, following administration of quinapril. Tissue ACE inhibition may be an important component of the mechanism of action of quinapril (and other ACE inhibitors) in achieving favourable effects in cardiovascular disorders. Quinaprilat has a short elimination half-life (approximately 2 hours), but binds potently to and dissociates slowly from ACE, thus allowing once or twice daily administration of quinapril in the treatment of patients with hypertension or congestive heart failure. Quinapril 10 to 40 mg/day has achieved adequate control of blood pressure in most patients with essential hypertension in clinical trials. Some patients required quinapril dosages up to 80 mg/day and/or concomitant diuretic therapy. Titrating quinapril dosages from 10 to 40 mg/day increased response rates without increasing the incidence or severity of adverse events. Addition of hydrochlorothiazide to quinapril therapy improved response rates by approximately 10 to 20% in patients with hypertension. In general, blood pressure control with quinapril monotherapy was similar to that achieved with enalapril or other standard antihypertensive agents in comparative trials. Quinapril < or = 40 mg/day improved exercise tolerance, reduced the severity and frequency of symptoms, and improved functional (New York Heart Association) class in most clinical studies of patients with congestive heart failure. In addition, beneficial haemodynamic and echocardiographic changes achieved with quinapril were maintained for up to 1 year with continued administration to such patients, but its effect on survival in patients with congestive heart failure has not been reported. The tolerability profile of quinapril is broadly similar to that of other ACE inhibitors; pooled data from clinical trials indicated that 12% of patients with hypertension or congestive heart failure receiving quinapril experienced a treatment-related adverse effects compared with 15% of enalapril recipients and 16% of captopril recipients. Thus, quinapril has clearly established a role as an effective and well tolerated alternative to other ACE inhibitors for the treatment of hypertension and congestive heart failure. While effects of quinapril on survival of patients with congestive heart failure have not been determined, large intervention studies have demonstrated improved mortality rates with other ACE inhibitors. Further studies, including a large ongoing trial of normotensive patients with coronary artery disease but normal left ventricular function, may also establish a role for quinapril in treating patients with ischaemic heart disease.

Administration, Oral↗
PubMed1996

Preservation of left ventricular mechanical function and energy metabolism in rats after myocardial infarction by the angiotensin-converting enzyme inhibitor quinapril.

We tested whether angiotensin-converting enzyme (ACE) inhibitor therapy with quinapril prevents the deterioration of mechanical function and high-energy phosphate metabolism that occurs in chronically infarcted heart. Rats were subjected to ligation of the left anterior descending coronary artery (LAD) or sham operation. Four groups were studied: sham-operated rats (n = 10), rats with myocardial infarction (MI, n = 9), sham-operated quinapril-treated rats (n = 8), and infarcted quinapril-treated (n = 13) rats. Treated rats received 6 mg/kg/day of the ACE inhibitor quinapril orally, initiated 1 h after MI or sham operation. Eight weeks after LAD ligation or sham operation, hearts were isolated and buffer-perfused isovolumically. High-energy phosphate metabolism and intracellular pH were continuously recorded with 31P-nuclear magnetic resonance (NMR) spectroscopy. Hearts were subjected to 15-min control, 30-min hypoxia (95% N2/5% CO2, and 30-min reoxygenation. Left ventricular developed pressure (LVDP) was reduced in infarcted hearts (58 +/- 10 vs. 98 +/- 9 mm Hg in sham, p < 0.05), and this reduction was partially prevented by quinapril (78 +/- 8 mm Hg). ATP content of residual intact myocardium after sham operation or MI was unchanged. Creatine phosphate was reduced in infarcted hearts (107 +/- 10 vs. 138 +/- 5% of control ATP, p < 0.05), and quinapril prevented this decrease (131 +/- 8%). Therefore, quinapril preserved both function and high-energy phosphate metabolism in the chronically infarcted heart. However, when hearts were subjected to acute hypoxia, susceptibility to acute metabolic stress was substantially increased in both quinapril-treated groups: ATP content at end-hypoxia was reduced to 31 +/- 7 and 37 +/- 6% in sham and infarcted quinapril-treated groups, whereas ATP in untreated sham and infarcted hearts was 66 +/- 6 and 66 +/- 3% of baseline values (p < 0.05 untreated vs. quinapril treated). Likewise, recovery of LVDP during reoxygenation was impaired by quinapril treatment (15 +/- 7 and 15 +/- 4 mm Hg in quinapril-treated sham and MI vs. 73 +/- 9 and 46 +/- 9 mm Hg in untreated sham and MI groups, p < 0.05 untreated vs. quinapril treated). The most likely explanation for the unexpected finding of increased susceptibility to acute metabolic stress in the quinapril-treated groups is reduced wall thickness leading to increased wall stress. The preservation of high-energy phosphate content in residual intact hearts after MI may contribute to the beneficial effects of ACE inhibitors after MI.

Adenosine Triphosphate↗
PubMed2000

Inhibition of arterial thrombogenesis by quinapril but not losartan.

The cardioprotective effect of angiotensin converting enzyme (ACE) inhibitors and angiotensin type I (AT1) receptor blockers may relate to their antithrombotic effect. We determined the differential effects of the ACE inhibitor quinapril and the AT1 receptor blocker losartan on arterial thrombus formation in the rat. Sprague-Dawley rats were fed regular chow or chow mixed with low-dose quinapril (0. 6 mg/kg/day), high-dose quinapril (1.2 mg/kg/day), or losartan (10 mg/kg/day) for 15 days. Abdominal aorta was exposed and wrapped with Whatman paper impregnated with 29% FeCl(3) (ferric chloride). Time to occlusive thrombus formation and weight of the thrombus were recorded. Aortic superoxide anion generation, platelet aggregation, plasma angiotensin II levels, and morphology of the thrombus were also examined. Both losartan and quinapril caused similar reductions in arterial pressure. Losartan did not affect the time to thrombus formation, whereas quinapril (both low and high doses) delayed the time to thrombus formation (P<.01 vs control). Weight of the thrombus was similar in all groups of rats. Platelet aggregation was inhibited by approximately 50 in both quinapril- and losartan-treated rats. The high-dose quinapril-treated rats showed markedly reduced vascular superoxide anion generation compared with the control rats (P<.05). Plasma angiotensin II levels were unaffected by quinapril treatment but were elevated 7-fold in losartan-treated rats (P <.001 vs. control rats). The thrombi in the control rats consisted of platelet aggregates, fibrin, and red blood cells. The intravascular platelet aggregates were much smaller in the quinapril-treated rats (P<.05 vs. control), but were similar in control and losartan-treated rats. In conclusion, quinapril but not losartan prolongs time to arterial thrombus formation and results in smaller platelet aggregates in the thrombus. Both quinapril and losartan decrease platelet aggregation, but only quinapril decreases superoxide anion generation. This effect on superoxide anion generation as well as mechanisms other than AT1 receptor blockade may underlie the salutary effect of quinapril on arterial thrombogenesis.

Angiotensin II↗
PubMed1991

Quinapril: a new second-generation ACE inhibitor.

Quinapril is a new non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor. The drug undergoes hepatic hydrolysis into its major active diacid metabolite, quinaprilat, and two minor inactive metabolites. On a weight basis quinaprilat is three times as potent an ACE inhibitor as quinapril. Approximately 60 percent of an oral dose of quinapril is absorbed. In contrast with captopril, the absorption of quinapril is unaffected by food. Peak serum concentrations of quinapril and quinaprilat are achieved within one and two hours, respectively. Approximately 61 percent of an orally administered dose is excreted in the urine, principally as quinaprilat. The elimination half-life of quinaprilat is three hours, but is prolonged up to 11 hours in patients with renal dysfunction. Quinapril dose reduction is recommended in patients with a creatinine clearance of 0.50 mL/sec or less. In the elderly the elimination of quinaprilat is reduced and correlates well with renal function. In patients with cirrhosis the hydrolysis of quinapril to quinaprilat is impaired resulting in lower plasma quinaprilat concentrations and up to a two-fold increase in quinapril half-life. Quinaprilat has a strong binding capacity to tissue ACE allowing for once-daily dosing. The recommended starting dose for quinapril is 20 mg/d. The nature and incidence of adverse reactions to quinapril are similar to those of enalapril and captopril. Quinapril's antihypertensive efficacy is equal to that of captopril and enalapril. A small number of patients with congestive heart failure (CHF) have been treated with quinapril. Preliminary data indicate that quinapril is an equally effective therapeutic alternative to presently available ACE inhibitors in the treatment of CHF.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

[Does quinapril improve coronary vasoconstriction in vasospastic angina?].

OBJECTIVES: Endothelial dysfunction is one of the important mechanisms of coronary spasm. Recently, the angiotensin converting enzyme (ACE) inhibitor quinapril, which has a high affinity for vascular ACE, has improved endothelial dysfunction in coronary artery disease. This study investigated whether quinapril improves coronary vasoconstriction induced by acetylcholine in vasospastic angina. METHODS: Twenty-four patients with vasospastic angina without significant organic stenosis diagnosed by the acetylcholine provocation test (vessel with spasm defined as > or = 90% stenosis provoked with chest pain and/or ischemic ST change) were enrolled in this study. Patients were randomly assigned to 2 groups: the quinapril group (receiving quinapril 20 mg/day, n = 12), and the non-quinapril group (not receiving quinapril, n = 12). All patients received calcium antagonist. Six months later, coronary angiography was repeated and changes in coronary spasm were compared between the groups. Seven patients were withdrawn from this study, so 17 patients were evaluated (the quinapril group: 8 patients, the non-quinapril group: 9). RESULTS: Angina symptoms were completely or almost suppressed in all patients during the study period. Angiographically, the number of patients with improvement of spasm, patients with deterioration of spasm and patients with stability of spasm were 1, 0, 7 in the quinapril group versus 0, 1, 8 in the non-quinapril group, respectively. There was no significant change between the 2 groups. Quantitative angiographic analysis showed that the coronary spasm rate (percentage of minimal lumen diameter at the site of spasm after administration of acetylcholine to minimal lumen diameter after administration of isosorbide dinitrate) at the first and second angiography were 71 +/- 10% and 62 +/- 21% in the quinapril group versus 73 +/- 14% and 67 +/- 15% in the non-quinapril group, respectively. There were no significant interval changes between the 2 groups (p = 0.60). CONCLUSIONS: Our results did not indicate that quinapril had improved coronary vasoconstriction induced by acetylcholine in patients with vasospastic angina.

Acetylcholine↗
PubMed1990

Pharmacokinetics of quinapril and its active metabolite, quinaprilat, in patients on chronic hemodialysis.

The pharmacokinetics of quinapril and its active metabolite, quinaprilat, were evaluated in 12 patients with end-stage renal disease (ESRD) on chronic hemodialysis. Each subject received a single 20-mg oral dose of quinapril 4 hours before a 4-hour hemodialysis treatment. Serial dialysate and blood samples were obtained over 4 and 96 hours, respectively. Samples were analyzed for quinapril and quinaprilat concentrations by gas chromatography. Mean tmax and Cmax values for quinapril were 1.2 hours and 129 ng/mL, respectively. Only one patient had detectable quinapril dialysate concentrations which accounted for 2.8% of the quinapril dose. Mean apparent plasma clearance for quinapril was 1275 mL/min with a mean half-life of 1.7 hours. Quinapril was extensively de-esterified to its diacid metabolite, quinaprilat. Mean tmax and Cmax for quinaprilat were 4.5 hours and 671 ng/mL, respectively. Mean apparent plasma clearance for quinaprilat was 24.0 mL/min with a mean half-life of 17.5 hours. As with quinapril, quinaprilat was not readily dialyzable. Only 5.4% of the administered quinapril dose was recovered as quinaprilat during a single hemodialysis treatment. In view of these results, supplemental quinapril doses need not be routinely given to patients following hemodialysis. Overall, quinapril and quinaprilat pharmacokinetics in patients with ESRD on chronic hemodialysis were not markedly different from those previously observed in patients with moderate to severe renal dysfunction (CLcr less than 29 mL/min) not yet requiring hemodialysis (RDND).

Adult↗
PubMedDate not supplied

Effects of the angiotensin-converting enzyme inhibitor quinapril on renal function in rats.

Angiotensin-converting enzyme inhibitors induce hypertrophy of renal juxtaglomerular cells in laboratory animals, and, in some studies, also produced renal tubular lesions. The objective of the present study was to evaluate the effects of the new angiotensin-converting enzyme inhibitor quinapril on renal function in normotensive rats. Male rats were dosed orally with quinapril at 0 (vehicle control) or 400 mg/kg for 1, 3, 8, 17 or 29 days. This dose of quinapril is more than 1000-fold greater than the effective antihypertensive dose in rats. Parameters of renal function were measured approximately 24 hours after dosing in order to minimize interference from acute pharmacologically mediated effects. Mean arterial blood pressure was only mildly affected at this time: 126.7 +/- 6.0 and 100.0 +/- 8.7 mm/Hg (mean +/- S.E.; day 29) for the control and quinapril-treated animals, respectively. Microscopic analysis of kidney tissue showed pronounced juxtaglomerular cell hypertrophy and hypergranularity in the quinapril-treated animals. These changes were first observed on day 7 and reached a maximum response by day 14. There were no morphologic changes in renal tubules. Quinapril had no significant effect on serum biochemistry parameters (electrolytes, urea nitrogen, creatinine). Urine output in quinapril-treated animals was increased 65% to 197% over controls during the course of the study and correlated with increased water consumption (r = 0.96). Urine osmolality was reduced 31% to 55% on days 8, 17 and 29. However, except for minimal reductions (< 15%) on day 8, there were no significant effects of quinapril on total (24 hour) urinary excretion of electrolytes or creatinine. There were also minimal effects of quinapril on direct measurements of renal function in anesthetized animals. Mean values (+/- S.E.) for control and quinapril-treated animals on day 29 were, respectively: glomerular filtration rate: 2.93 +/- 0.37 and 2.70 +/- 0.53 ml/min; effective renal plasma flow: 11.14 +/- 2.06 and 11.22 +/- 2.35 ml/min; effective renal tubular secretion: 267 +/- 63 and 261 +/- 106 micrograms/min; filtration fraction: 27.1 +/- 2.5 and 24.0 +/- 0.4%; and fractional sodium excretion: 0.25 +/- 0.04 and 0.34 +/- 0.04%. There were also no significant differences between control and quinapril-treated animals when the above parameters were measured following plasma volume expansion on day 29. The results show that quinapril had no adverse effects on renal function in rats when administered at a suprapharmacological dose for up to 4 weeks.(ABSTRACT TRUNCATED AT 400 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Quinapril--a preclinical review of the pharmacology, pharmacokinetics, and toxicology.

Quinapril is an orally active, non-peptide, nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor that acts potently and specifically to interrupt the conversion of angiotensin I to angiotensin II in both plasma and tissue. Quinapril is enzymatically hydrolyzed to a pharmacologically active diacid form quinaprilat. Quinapril is efficacious in hypertensive models exhibiting both high (renal hypertensive rats, diuretic-treated dogs) and normal (spontaneously hypertensive rats) plasma renin activity. Quinapril does not prevent the development of hypertension when plasma renin activity (PRA) is markedly suppressed as in the deoxycorticosterone-saline treated rat. Hemodynamic studies in dogs indicate that quinapril decreases total peripheral and renal vascular resistance. Quinaprilat produces natriuresis and mild diuresis at doses that do not alter mean arterial blood pressure. Quinapril has the potential to affect plasma lipids beneficially or at least be "lipid neutral." Oral absorption of quinapril is rapid in rats, dogs, and monkeys. There is rapid and extensive distribution of radiolabel to most tissues except brain. Plasma radiolabel concentration-time profiles exhibit polyexponential decay with a prolonged terminal phase at low concentrations in all species. Metabolism to compounds other than quinaprilat is not extensive. Quinapril is excreted primarily as quinaprilat and to a lesser degree as quinapril. Quinapril is well tolerated in a variety of pharmacologic safety screens and its toxicity profile is similar to that of other ACE inhibitors. Quinapril does not adversely affect reproduction; it is not teratogenic, carcinogenic, or mutagenic.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Clinical pharmacology of quinapril in healthy volunteers and in patients with hypertension and congestive heart failure.

Quinapril is converted to quinaprilat, a long-acting angiotensin converting enzyme (ACE) inhibitor, and is currently being studied for the treatment of hypertension and congestive heart failure. In studies of healthy volunteers, single quinapril doses of 0.625 mg to 80 mg inhibited plasma ACE activity for up to forty-eight hours. Dose-related inhibition of angiotensin I pressor response occurred after administration of quinapril doses of 0.625 mg to 20 mg. In addition, plasma renin activity increased and aldosterone and angiotensin II concentrations decreased following single or multiple doses of quinapril. Subsequently, dose-ranging studies were conducted in patients with mild to moderate hypertension and congestive heart failure. Pilot studies suggested that 5 mg of quinapril given once daily had minimal antihypertensive effect. Therefore, a definitive, multiple-dose, placebo-controlled, double-blind study of 5, 10, and 20 mg once daily doses of quinapril was performed. Quinapril doses of 10 mg and 20 mg were statistically significantly superior to placebo (p less than 0.05) in lowering sitting diastolic blood pressure (DBP), whereas 5 mg of quinapril had only marginal clinical effectiveness. A twenty-four-hour blood pressure monitoring study indicated that quinapril administered once or twice daily effectively lowered DBP in patients with mild to moderate hypertension. This study suggested, however, that some patients may not achieve sustained reductions in DBP over the entire twenty-four-hour interval with quinapril administered once daily and may require twice daily therapy. In studies of patients with refractory congestive heart failure, acute favorable hemodynamic effects were demonstrated after the administration of quinapril.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

A postmarketing surveillance evaluation of quinapril in 3742 Canadian hypertensive patients: the ACCEPT Study. Accupril Canadian Clinical Evaluation and Patient Teaching.

The Accupril Canadian Clinical Evaluation and Patient Teaching (ACCEPT) study was a multicenter, 6-month, open-label, postmarketing surveillance study where the efficacy and safety of quinapril, an angiotensin-converting enzyme (ACE) inhibitor, was evaluated in a general population of patients with essential hypertension. Participating physicians followed their normal office procedures for the initiation of quinapril therapy (a dose of 10 mg QD in the majority of cases). The dose was titrated to blood pressure response, generally at 2-week intervals, for a maintenance dose of 10 mg QD to 20 mg QD in most cases (86% at 6 months) and not to exceed 40 mg QD. The use of concomitant antihypertensive medications was left to the discretion of the physician. By random assignment, physicians obtained patient informed consent on either a detailed form that listed possible quinapril side effects or a less specific form, which did not list particular side effects. The purpose of using two different forms was to assess any potential association between the frequency of adverse-event reporting and patient's awareness of quinapril side effects. The patients also received an educational package that provided general information on hypertension and lifestyle modifications known to reduce cardiovascular risk factors. An intent-to-treat analysis included data from 3742 patients in whom the median age was 56 years and the median duration of hypertension was 5 years. The demographic characteristics of these patients were similar to those identified in Canadian hypertensive patients in a recent population-based survey. Nearly 80% of the ACCEPT study patients had more than one cardiovascular risk factor, in addition to hypertension. Among 2979 patients receiving quinapril at 3 months, 77% were stabilized. Among 2517 patients continuing to receive quinapril at 6 months, 84% were stabilized. Greater declines in both diastolic and systolic blood pressures were evident among patients who continued to receive quinapril as part of an antihypertensive regimen than among those who discontinued quinapril treatment. Blood pressure responses to quinapril were similar in newly diagnosed patients and those with a history of hypertension. A total of 980 patients (26.2%) reported one or more adverse events. Cough was most frequently reported and was deemed as definitely related to quinapril therapy by the treating physician in 3.6% of cases. Serious adverse events occurred in 55 patients (1.5%) and were assessed as possibly related to quinapril in only three patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1995

[A comparative study of the efficacy of lisinopril versus quinapril in controlling light to moderate arterial hypertension. A follow-up with ABPM].

OBJECTIVE: To compare the antihypertensive efficacy of lisinopril versus quinapril given 20 mg once daily for the treatment of mild to moderate arterial hypertension (I-II WHO grades) using ambulatory blood pressure monitoring. This study also investigated the tolerance, adverse effects and changes in haematological or biochemical parameters with both drugs. METHODS: Fifty patients (men and women) with a range of age between 18 to 75 years were included in this open, randomized study to assess the hypotensive efficacy of lisinopril versus quinapril after 2 months of treatment, using ambulatory blood pressure monitoring (ABPM). To study data obtained from ABPM Mc Call curves were used and statistical analysis was made using Epistat programme. Covariance and Chi-square test were used for the comparative analysis of different variables, considering as statistically significant the value p < 0.05. Graphics were made using Lotus 123, V 3.0 version. All patients gave their informed consent to participate in the study. The protocol was approved by the Ethical Committee of the Clínico Hospital. RESULTS: Systolic blood pressure decreased from 172.6 to 152.6 mmHg in the lisinopril group (p < 0.001) and from 171.6 to 147 mmHg in the quinapril group (p < 0.001). Diastolic blood pressure decreased from 105.6 to 86.8 mmHg in the lisinopril group (p < 0.001) and from 106.1 to 88.1 mmHg in the quinapril group (p < 0.05). Using ABPM mean systolic blood pressure decreased from 157.3 to 126.5 mmHg with lisinopril (p < 0.001) and from 148 to 137.4 mmHg with quinapril (p < 0.05). Mean diastolic blood pressure decreased from 93.6 to 81.7 mmHg with lisinopril (p < 0.001) and from 89.4 to 85.9 with quinapril (p < 0.05). Decreases in basal glycemia were found from 0.996 to 0.878 in quinapril group (p < 0.05), total quinapril cholesterol in both groups (from 228.7 to 207.2 with lisinopril and from 247.4 to 225.7 with quinapril) (p < 0.05) and cholesterol-LDL in the quinapril group (180.1 to 152.1) (p < 0.05). CONCLUSIONS: Both drugs produce a fall of blood pressure in mild-to-moderate hypertension, although using ABPM this fall is more significant with Lisinopril. According to Mc Call index 73.4% of patients in the lisinopril group and 62.7% of quinapril group controlled their hypertension, and a difference found between BP values obtained in the clinic and those obtained using ABPM.

Adolescent↗
PubMed1990

Quinapril: overview of preclinical data.

Quinapril hydrochloride, a new, orally active, nonpeptide, nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor, has been studied extensively in a variety of in vitro and in vivo animal models. Quinapril inhibits the contractile and pressor effects of angiotensin I in rabbit aorta and in rats, respectively, and lowers blood pressure in both high- and normal-renin rodent and diuretic-treated dog models of hypertension. No tolerance to the antihypertensive effects of quinapril was noted in spontaneously hypertensive rats treated with quinapril for up to 14 consecutive days. As with other ACE inhibitors, quinapril had virtually no effect on the development of hypertension in the renin-independent one-kidney deoxycorticosterone (DOCA)-salt hypertensive rat. Antihypertensive activity best correlates with the inhibition of tissue (vascular) ACE, and thus the reduction in peripheral vascular resistance associated with plasma and tissue ACE most likely accounts for the therapeutic benefit of quinapril. Preliminary data from a trial of quinapril in cardiomyopathic hamsters show that the drug prevents the anticipated decline in left ventricular contractile function and retards the temporal progression of left ventricular failure. ACE inhibitors have been found to have a lipid-neutral profile, unlike some other classes of antihypertensives. Quinapril is rapidly absorbed and extensively distributed to all tissues except brain. It is rapidly hydrolyzed to quinaprilat, its pharmacologically active diacid form. Metabolism to other compounds is not extensive. Quinapril's preclinical toxicologic profile is similar to that of other ACE inhibitors. Long-term toxicology studies show that quinapril is not teratogenic, carcinogenic, or mutagenic.

Aged↗
PubMed1991

Hemodynamic and morphological effects of quinapril during genetic hypertension development.

The relative contributions of the hemodynamic and morphological (vascular and cardiac) modifications induced by long-term administration of an angiotensin I-converting enzyme inhibitor, quinapril, to the drug's long-lasting preventive effects vis-à-vis genetic hypertension development (GHD) have been investigated in young spontaneously hypertensive rats (SHRs). Two groups of SHRs were given quinapril (10 mg/kg/day) or distilled water from 5 to 20 weeks of age. The drug was then stopped, but observations continued for another 7 weeks. At selected times systemic and regional hemodynamic parameters as well as cardiac and vascular morphological effects were investigated. During the treatment period, quinapril partially opposed GHD and limited the early rise in total peripheral and regional vascular resistances observed in control animals. Quinapril's partial preventive effect vis-à-vis GHD persisted, but faded after treatment withdrawal. From a morphological point of view, quinapril strongly opposed aortic wall hypertrophy as evidenced by significant reductions in media thickness and wall to lumen ratio and by a significant increase in aortic nuclear density. Quinapril also limited vascular fibrosis development. At the cardiac level, quinapril reduced heart weight to body weight ratio and opposed myocardial hypertrophy and cardiac collagen synthesis. All these vascular and cardiac morphological changes were delayed (starting after 9-15 weeks of treatment) as compared to quinapril's hemodynamic effects. Finally, the drug's vascular and cardiac antihypertrophic properties persisted after treatment withdrawal. In conclusion, our data indicate that the early systemic and regional hemodynamic effects of quinapril initiate its antihypertensive action, but the drug-induced delayed and prolonged vascular morphological changes later take over and may be partly responsible for quinapril's residual blood pressure lowering effects after treatment withdrawal.

Animals↗
PubMed1998

Analysis of the pharmacokinetic interaction between cephalexin and quinapril by a nonlinear mixed-effect model.

Oligopeptidic drugs such as beta-lactams and angiotensin-converting enzyme inhibitors share the same carriers in humans and animals, which results in possible pharmacokinetic interactions. To model such interactions, the effects of quinapril on cephalexin pharmacokinetics were investigated in rats. Blood cephalexin concentrations were measured by liquid chromatography, and the data were analyzed by a noncompartmental method and by fitting a bicompartmental model by a nonlinear mixed-effect modeling approach. Five groups of eight rats were examined. In the first three groups, cephalexin elimination kinetics after intra-arterial administration alone or in combination with quinapril given by the parenteral or the oral route were studied, and the occurrence of a pharmacokinetic interaction was not revealed. The absence of an effect of quinapril on cephalexin elimination after parenteral administration might be explained either by the higher affinity of cephalexin for the renal anionic transport system than that of quinapril or by the much higher concentrations of cephalexin than those of quinapril. In the last two groups, cephalexin was administered by the oral route alone or in combination with quinapril. The mean area under the concentration-time curve (AUC) for cephalexin was increased by ca. 30% by coadministration of quinapril (40.1 versus 31.4 mg.h/liter; P = 0.04). The mean elimination clearance of cephalexin was significantly decreased by quinapril, from 0.81 to 0.64 liter/h/kg of body weight (P < 0.05), probably by competitive inhibition of cephalexin secretion at the tubular level. The mean absorption rate constant of cephalexin was significantly lowered by quinapril (from 0.249 to 0.177 h-1; P < 0.01), without modification of the extent of absorption (89%). This pharmacokinetic interaction could be explained by competitive inhibition of cephalexin active transport by quinapril at the intestinal level.

Angiotensin-Converting Enzyme Inhibitors↗