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Aims/hypothesis: High sodium (HS) effects on hypertension are well established. Recent evidence implicates a relationship between HS intake and insulin resistance, even in the absence of hypertension. The aim of the current study was to determine whether loss of the vascular actions of insulin may be the driving factor linking HS intake to insulin resistance. Methods: Sprague Dawley rats were fed a control (0.31% wt/wt NaCl) or HS (8.00% wt/wt NaCl) diet for 4 weeks and subjected to euglycaemic-hyperinsulinaemic clamp (10 mU min kg) or constant-flow pump-perfused hindlimb studies following an overnight fast. A separate group of HS rats was given quinapril during the dietary intervention and subjected to euglycaemic-hyperinsulinaemic clamp as above. Results: HS intake had no effect on body weight or fat mass or on fasting glucose, insulin, endothelin-1 or NEFA concentrations. However, HS impaired whole body and skeletal muscle glucose uptake, in addition to a loss of insulin-stimulated microvascular recruitment. These effects were present despite enhanced insulin signalling (Akt) in both liver and skeletal muscle. Constant-flow pump-perfused hindlimb experiments revealed normal insulin-stimulated myocyte glucose uptake in HS-fed rats. Quinapril treatment restored insulin-mediated microvascular recruitment and muscle glucose uptake in vivo. Conclusions/interpretation: HS-induced insulin resistance is driven by impaired microvascular responsiveness to insulin, and is not due to metabolic or signalling defects within myocytes or liver. These results imply that reducing sodium intake may be important not only for management of hypertension but also for insulin resistance, and highlight the vasculature as a potential therapeutic target in the prevention of insulin resistance. [ABSTRACT FROM AUTHOR]

We studied the effects of three various angiotensin converting enzyme inhibitors (enalapril, lisinopril and quinapril) on heart rhythm variability in anesthetized and immobilized rats. In all cases (except for quinapril in experiments on anesthetized animals), the preparations reduced the total rhythm variability and, according to spectrum analysis, increased activity of the parasympathetic autonomic nervous system to different degrees and decreased sympathetic tone. Quinapril and lisinopril produced the most pronounced influence on heart rhythm in anesthetized rats; enalapril was less potent in this respect. In immobilized animals, quinapril and enalapril showed the greatest activity and lisinopril the lowest. The more pronounced effect of quinapril both under anesthesia and during immobilization appears to be linked to the highest affi nity of quinaprilat to circulatory and tissue compartments of the renin-angiotensinaldosterone system. [ABSTRACT FROM AUTHOR]

Several antihypertensive drugs belonging to the group of ACE inhibitors have been selected for testing their nootropic activity based on a computer-aided prediction of their biological activity spectra using the PASS computer program package. Experiments were conducted on mice by the spontaneous orientation test (patrolling behavior) in a cross-maze. It was found that perindopril at a dose of 1 mg/kg in addition to quinapril and monopril at a dose of 10 mg/kg improved the patrolling behavior in the cross-maze test. This effect is similar to the effects of the standard nootropic drugs piracetam and meclofenoxate (at doses of 300 and 120 mg/kg, respectively). The observed nootropic effect of some ACE inhibitors is likely to be unrelated to their antihypertensive effect since the nootropic action took place only at relatively low doses of perindopril, quinapril, and monopril and was not observed with further increase of the dose. The identification of nootropic action of antihypertensive drugs that are commonly used in clinical practice leads to their new clinical applications with allowance for the relevant idiosyncrasies of patients. [ABSTRACT FROM AUTHOR]

unified HPLC method for analyzing the angiotensin-converting enzyme (ACE) inhibitors perindopril, lisinopril, and quinapril using a single column with a nonpolar phase based on octadecylsilica gel and a universal eluant (a mixture of acetonitrile and aqueous heptanesulfonic acid and triethylamine) is described; this method significantly decreases workload and the cost of analysis. The method can be used for the analysis of substances and different therapeutic formulations containing ACE inhibitors. [ABSTRACT FROM AUTHOR]

P-wave dispersion (PWD) has been shown to be a non-invasive electrocardiographic predictor for development of atrial fibrillation (AF). Thus, it may be possible to attenuate AF risk through improvement of PWD. In this study, we compared the effects of an angiotensin-converting enzyme (ACE) inhibitor, quinapril, and an angiotensin receptor blocker (ARB), irbesartan, on PWD. A total of 38 newly diagnosed hypertensive patients were enrolled in the study. The patients were randomly assigned to receive treatment with either irbesartan (150–300 mg) or quinapril (20–40 mg). P-wave durations and PWD were measured at baseline and after 6 and 12 months of treatment. Echocardiographic examinations were performed at baseline and after 12 months of treatment. Both drugs significantly reduced blood pressure to a similar degree ( P<0.001). Deceleration time (both P<0.001) and isovolumetric relaxation time (both P=0.007) were also significantly reduced, whereas there was no significant change in the early diastolic flow/atrial contraction signal ratio. Both irbesartan and quinapril significantly decreased maximum P-wave duration (Pmax) ( P<0.001 and P=0.002, respectively) and PWD (from 68.0±22.1 to 41.0±25.1 msec for irbesartan, and from 70.5±20.4 to 46.6±13.3 msec for quinapril; both P<0.001). Baseline and follow-up blood pressure, heart rate, echocardiographic findings, and P-wave values were not significantly different between the irbesartan and quinapril groups. No patient developed AF during follow-up. There was no significant correlation between PWD and blood pressure or diastolic function parameters. Antihypertensive treatment with either irbesartan or quinapril is associated with significant reductions in Pmax and PWD. [ABSTRACT FROM AUTHOR]

BACKGROUND: and objective: Recently the PatenT (Prevalence, awareness, treatment and control of hypertension in Turkey) study showed that while the prevalence of hypertension in Turkey is high, effective control of BP is infrequently achieved. This study investigated the efficacy and safety of quinapril (as monotherapy or in combination with hydrochlorothiazide [HCTZ]) for achieving BP control (target <140/90mm Hg) in Turkish subjects with mild to moderate hypertension. METHODS: Two-hundred male and female outpatients aged 19–65 years with mild to moderate hypertension (stage I or II, Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure 7 guidelines) entered this 12-week, open-label study. All subjects received quinapril 20 mg/day for 6 weeks. If BP targets were achieved at week 6, responders were maintained on 20 mg/day; if BP targets were not achieved, non-responders were randomised to quinapril 40 mg/day or quinapril 20 mg/day + HCTZ 12.5 mg/day for the remainder of the study. RESULTS: After 6 weeks, 63% of subjects achieved BP targets, and 82% of week-6 responders who continued on quinapril 20 mg/day maintained BP targets at week 12. Of the non-responders, 50% and 52% randomised to quinapril 40 mg/day or quinapril 20 mg/day + HCTZ 12.5 mg/day, respectively, went on to achieve BP targets by week 12. Safety was not compromised with increased dosages or use of combination therapy. CONCLUSION: Quinapril was an effective and safe treatment for achieving and maintaining recommended BP targets in this sample population. These findings will provide clinicians in Turkey with valuable data on the use of quinapril for effective control and management of hypertension. [ABSTRACT FROM AUTHOR]

The effects of chronic treatment with quinapril on blood pressure, vascular reactivity and structure of resistance arteries were examined in adult, male spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. SHR and WKY at 15 weeks of age were treated with quinapril (10 mg/kg per day) for 10 weeks. Structural changes in the mesenteric arteries were measured by optical sectioning with confocal microscopy and in renal arteries by light microscopic measurements. Apoptotic cells in the mesenteric vessel wall were identified using the terminal deoxynucleotide transferase-mediated dUTP-nick end-labelling (TUNEL) method. The response of mesenteric arteries to noradrenaline, electrical stimulation, acetylcholine and sodium nitroprusside was studied using a pressure myograph system. Treatment with quinapril significantly lowered systolic blood pressure and ventricular weight in both SHR and WKY. It reduced wall thickness and medial volume in mesenteric arteries from SHR and WKY and media-to-lumen ratio in interlobular arteries of SHR. It also decreased the number of smooth muscle layers in SHR and increased the number of apoptotic smooth muscle cells in both SHR and WKY. In addition, treatment normalized the augmented contractile responses and improved the impaired relaxation response of SHR mesenteric arteries to the level of WKY. We conclude that treatment with quinapril lowered blood pressure and improved cardiac and vessel structure and vessel function. An increase in apoptotic process of medial smooth muscle cells is one of the mechanisms underlying the vascular structural improvement. [ABSTRACT FROM AUTHOR]

Summary: Quinapril is rapidly de-esterified after absorption to quinaprilat (the active diacid metabolite), a potent angiotensin converting enzyme (ACE) inhibitor. Quinapril produces favourable haemodynamic changes, and improves ventricular and endothelial function in patients with various cardiovascular disorders; these effects are mediated through the binding of quinaprilat to both tissue and plasma ACE. Quinapril 10 to 40 mg/day provided effective blood pressure control in most patients with essential hypertension in clinical trials, but some patients required dosages of 80 mg/day and/or concomitant diuretic therapy. In general, quinapril provided similar blood pressure control to other standard antihypertensive therapies including other ACE inhibitors, calcium antagonists and β-adrenoceptor antagonists in comparative clinical trials. Combined therapy with quinapril and hydrochlorothiazide had a significantly greater antihypertensive effect than either drug as monotherapy in two well designed studies. Quinapril has also been shown to reduce microalbuminuria in patients with hypertension and/or diabetes mellitus. In patients with congestive heart failure, quinapril ≤40 mg/day produced beneficial haemodynamic and echocardiographic changes and improved exercise tolerance, symptoms and functional class. Effects of quinapril on survival have not been investigated, but quinapril 10 to 20 mg/day showed comparable efficacy to captopril 25 to 50mg twice daily in two well designed trials. In patients with coronary artery disease, quinapril 40 mg/day significantly reduced the incidence of ischaemic events after coronary artery bypass grafting (CABG) in a well controlled study (n = 148). However, a lower dosage of quinapril (20 mg/day) showed no effect on ischaemic events or atherosclerotic progression with 3 years of treatment in a similarly designed study involving 1750 patients undergoing coronary angioplasty. The tolerability of quinapril is similar to that of other ACE inhibitors. In placebo-controlled trials, cough occurred in 2 and4.3% and hypotension occurred in <1 and 2.9% of quinapril recipients with hypertension or congestive heart failure, respectively. No increase in adverse events was observed when the dosage was increased from 10 to 40 mg/day. Conclusion: Quinapril is now firmly established as an effective and well tolerated ACE inhibitor for the treatment of patients with hypertension and congestive heart failure. Quinapril 40 mg/day also significantly reduced the incidence of ischaemic events in patients undergoing CABG in one study; however, a lower dosage of quinapril (20 mg/day) had no effect on ischaemic events in patients undergoing coronary angioplasty in another trial. Additional trials in patients with coronary artery disease receiving optimal dosages of quinapril (40 mg/day) would be useful. Overview of Pharmacodynamic Properties: Quinapril is a non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor prodrug which is metabolised to quinapril at, the active diacid metabolite. As with all ACE inhibitors, quinaprilat exerts its therapeutic effect by inhibiting the conversion of angiotensin I to angiotensin II; ACE inhibitors also prevent the degradation of bradykinin, but whether increased levels of bradykinin play a role in the therapeutic effects of these agents is still uncertain. Quinaprilat binds with a high affinity to both plasma and tissue ACE. In humans, a single dose of quinapril 20mg provides >50% inhibition of plasma ACE over 24 hours. Quinapril has also been shown to inhibit angiotensin II formation in human vasculature following several weeks of administration. In humans, the hypotensive effect of exogenous bradykinin is potentiated by ACE inhibitor therapy, and the bradykinin antagonist icatibant reduces the hypotensive effect of ACE inhibitors in humans. Similar effects have been demonstrated with quinapril in animal studies. In patients with hypertension, once-daily administration of quinapril 10 to 40mg provided good 24-hour blood pressure control as assessed by ambulatory blood pressure monitoring in some, but not all studies. Generally, quinapril had no significant effect on heart rate, cardiac output or left ventricular (LV) ejection fraction. In patients with moderate to severe congestive heart failure, quinapril produced a number of favourable haemodynamic effects including improved cardiac output and reduced systemic vascular resistance and pulmonary capillary wedge pressure, without an increase in heart rate. Quinapril ≤40 mg/day reduced LV hypertrophy in patients with hypertension or chronic valvular regurgitation, and reduced progressive ventricular remodelling in patients with distant myocardial infarction in one small investigation. Quinapril 10 to 40mg once daily improved endothelial function (as measured by improved flow-mediated dilation or reduced vasoconstrictive response to acetylcholine) in patients with coronary artery disease and hypertension over 2 to 6 months of therapy; improved endothelial function was also observed in patients with congestive heart failure receiving a single infusion of quinaprilat. In contrast, the angiotensin II antagonist losartan (50 mg/day), calcium antagonists amlodipine (5 mg/day) and nitrendipine (10 mg/day), and the ACE inhibitor enalapril (10 mg/day) did not improve endothelial function. Quinapril 5 to 10 mg/day increased heart rate variability and reduced sympathetic overactivity after myocardial infarction in patients with coronary artery disease. In general, quinapril showed neutral or beneficial effects on lipid profiles, glycaemia and renal haemodynamics. Overview of Pharmacokinetic Properties: Following oral administration of quinapril in healthy volunteers, approximately 60% of the dose is absorbed and peak plasma concentration (C max) is reached within 1 hour. Quinapril then undergoes rapid de-esterfication to quinaprilat, the active diacid metabolite, which reaches C max within 2 hours. Both quinapril and quinaprilat are highly bound to plasma proteins (≈97%), and mean elimination half-lives are ≈1 and 2 hours, respectively. Quinaprilat has a long terminal half-life of ≈25 hours, which may be associated with its slow release from ACE. The main route of elimination is via the kidney: quinaprilat accounts for 30% of the oral dose recovered in the urine, quinapril accounts for 3% and two other inactive metabolites account for 6% each. The remainder of the oral dose is eliminated in the faeces as unabsorbed quinapril or by biliary excretion of quinapril and its metabolites. The pharmacokinetics of quinapril and quinaprilat are affected by renal and hepatic impairment. In addition, elimination of quinapril may be reduced in patients with congestive heart failure and/or advanced age; however, this reduction is typically a result of decreased renal function in these patients. In lactating mothers receiving a 20mg dose of quinapril, only 1.6% of the maternal dose was estimated to reach the infant. Therapeutic Efficacy: Hypertension The antihypertensive efficacy of quinapril is well documented, with dosages of 10 to 80 mg/day consistently producing significant reductions in blood pressure in patients with mild to moderate hypertension (patients with DBP 95 to 120mm Hg and/or SBP >140mm Hg) in placebo-controlled trials. In comparative, randomised clinical trials, quinapril (10 to 80 mg/day) displayed similar antihypertensive efficacy to other ACE inhibitors captopril (25 to 200 mg/day) and enalapril (10 to 80 mg/day), but inconsistent results have been reported in studies comparing quinapril with lisinopril (2.5 to 20 mg/day). Quinapril 20 to 40mg once daily showed similar efficacy to β-adrenoceptor antagonist atenolol 50 to 100 once daily; however, lower dosages of quinapril (10 to 20 mg/day) did not appear to be as effective as atenolol 50 to 100 mg/day in patients with a history of moderate to severe hypertension. Quinapril 10 to 40 mg/day produced similar response rates to metoprolol 50 to 200 mg/day in patients with hypertension, but quinapril 20 mg/day was slightly less effective than metoprolol 100 mg/day in reducing diastolic blood pressure in patients with type 2 diabetes mellitus in another study. Quinapril (5 to 40 mg/day) also showed similar antihypertensive efficacy to twice-daily sustained release nifedipine (20 to 80 mg/day), once-daily amlodipine (5 to 10 mg/day) and once-daily nitrendipine (10 to 40 mg/day). The addition of a diuretic [usually hydrochlorothiazide (HCTZ)] to quinapril monotherapy increases the response rate from ≥50% to ≈70 to 90% in patients with hypertension. Two large, randomised, double-blind studies showed that quinapril and HCTZ combination therapy was significantly more effective at lowering blood pressure than either drug as monotherapy over 8 weeks of treatment in patients with moderate to severe hypertension. Quinapril 10 to 40 mg/day reduced urinary albumin excretion rate (UAE) to a similar extent as captopril 50 to 150 mg/day and metoprolol 100 mg/day, and was significantly better than atenolol 50 to 100 mg/day and/or HCTZ 25 to 50 mg/day at reducing UAE in randomised, comparative trials. Quinapril 10 to 40 mg/day also significantly decreased UAE in patients with hypertension with or without type 2 diabetes mellitus in two noncomparative studies. Congestive Heart Failure In patients with congestive heart failure, quinapril ≤40 mg/day produced favourable haemodynamic and echocardiographic parameters and improved symptoms, exercise tolerance and disease severity. These favourable effects have been maintained for up to 1 year of nonblind therapy. Although the effect of quinapril on survival in patients with congestive heart failure has not been determined, treatment with other ACE inhibitors has resulted in improved mortality rates, and a recent meta-analysis suggests a class effect for these agents in reducing morbidity and mortality in these patients. In two recent double-blind, randomised, placebo-controlled investigations (n = 131 and 146), quinapril 10 to 20mg once daily showed comparable efficacy to captopril 25 to 50mg twice daily in reducing symptoms of heart failure (e.g. dyspnoea, ventricular gallop or pulmonary congestion), improving echocardiographic parameters (e.g. LV ejection fraction or LV diastolic/systolic diameters) and improving exercise tolerance in patients with mild to moderate congestive heart failure [New York Heart Association (NYHA) functional classes I to III] over 10 or 12 weeks of treatment. In one study, NYHA functional class was also improved with both therapies but quinapril had a greater effect than captopril in patients with more severe disease. Similar effects were observed in another study in elderly patients (aged ≥65 years) with NYHA functional class II or III with an aetiology of ischaemic heart disease. Coronary Artery Disease The results of two large, double-blind, placebo-controlled, randomised trials investigating the potential use of quinapril in patients with coronary artery disease have recently become available: the effects of QUinapril On Vascular Ace and Determinants of Ischemia (QUO VADIS) study and the QUinapril Ischemic Event Trial (QUIET). In the QUO VADIS trial (n = 148), a significant reduction in cardiac events was observed in patients receiving quinapril 40 mg/day versus placebo for 1 year following coronary artery bypass surgery. In contrast, in the QUIET trial, treatment with quinapril 20 mg/day over 3 years had no significant effect on reducing cardiac events or the progression of atherosclerosis in 1750 normolipidaemic, normotensive patients with normal LV function (LV ejection fraction >40%) following coronary angioplasty. Flaws in the design of the QUIET investigation, including insufficient sample size, inadequate quinapril dosage and use of lipidlowering therapy, may have contributed to the lack of effect seen with quinapril in this study. In other investigations in patients undergoing coronary angioplasty and/or coronary stent implantation, quinapril has shown some efficacy in reducing restenosis; however, additional trials are necessary to define the role of quinapril in these patients. Tolerability: Quinapril is generally well tolerated and adverse experiences are usually mild and transient and seldom require treatment withdrawal. In placebo-controlled trials in patients with hypertension or congestive heart failure, discontinuation of quinapril therapy because of adverse events was required in 4.7 and 6.8% of patients, respectively. The most commonly occurring adverse events seen in these studies were dizziness, headache, cough and fatigue, each occurring in <8% of patients. ACE inhibitor class-specific cough occurred in 2% of patients with hypertension and 4.3% of patients with congestive heart failure. Hypotension rarely occurred in patients with hypertension but was reported in 2.9% of patients with congestive heart failure in placebo-controlled trials. Angioedema was seen in 0.1% of patients. Quinapril shows similar tolerability to other ACE inhibitors. In a large meta-analysis of comparative clinical trials, 12% of 1819 patients receiving quinapril experienced a treatment-related adverse event compared with 15% of 339 enalapril recipients and 16% of 186 captopril recipients. Treatment withdrawal because of adverse events in these studies was less common in quinapril recipients (3.7%) than those receiving enalapril (8.0%) or captopril (6.4%). In addition, quinapril 10 to 40 mg/day showed similar tolerability to metoprolol 50 to 200 mg/day in a large comparative study. Elderly patients (aged >65 years) tolerated quinapril as well as younger patients (aged <65 years), and addition of a diuretic to quinapril therapy induced little change in incidence of adverse events. Dosage and Administration: In patients with hypertension, quinapril therapy is initiated at a once-daily dose of 10 or 20mg and titrated according to blood pressure response to a maximum of 80 mg/day. Twice-daily administration may be required in patients whose blood pressure control diminishes towards the end of a once-daily dosage interval. Because of the risk of hypotension, caution is advised when quinapril is added to diuretic therapy. European prescribing information recommends a low initial dose of quinapril (2.5mg) in patients already receiving diuretic therapy. US prescribing information recommends that patients should discontinue diuretic therapy 2 to 3 days prior to beginning quinapril treatment; if this is not feasible, the recommended initial dose of quinapril is 5mg. Lower starting dosages of quinapril are also recommended for elderly hypertensive patients (aged ≥65 years) and those with renal impairment. The quinapril dosage should then be gradually titrated to blood pressure control. In patients with congestive heart failure, quinapril is indicated for use as an adjunctive therapy in combination with diuretics and/or digitalis. The initial dose of quinapril recommended in the US and Europe is 5mg and 2.5mg, respectively. The quinapril dosage should then be titrated up to a maximum of 40 mg/day to achieve an effective dose or until the appearance of undesirable adverse events. In Europe, medical supervision is recommended during initiation of quinapril in patients with severe/unstable congestive heart failure, patients receiving high dose loop diuretics (e.g. >80mg furosemide), multiple diuretics or high dose vasodilator therapy, patients with hypovolaemia, hyponatraemia (serum sodium <130 mgEq/L), systolic blood pressure <90mm Hg or serum creatinine >150 μmol/L and those aged ≥70 years. In the US, it is recommended that all patients with congestive heart failure be supervised for at least 2 hours following the initial dose of quinapril to monitor for the development of hypotension. [ABSTRACT FROM AUTHOR]

Purpose. The objective of this study was to examine the effect of a citric acid-citrate buffer system on the chemical instability of lyophilized amorphous samples of quinapril hydrochloride (QHCl). Methods. Molecular dispersions of QHCl and citric acid were prepared by colyophilization from their corresponding aqueous solutions with a molar ratio of QHCl to citric acid from 1:1 to 6:1 and solution pH from 2.49 to 3.05. Solid samples were subjected to a temperature of 80°C and were analyzed for degradation using high-performance liquid chromatography. The glass transition temperature, Tg, of all samples was measured by differential scanning calorimetry. Results. Samples were first examined by varying the Tg and maintaining the initial solution pH constant. At pH 2.49 the rate of reaction was found to be less dependent on the sample Tg, whereas at pH ≥2.75 the rate decreased with an increase in Tg. In a second set of experiments at a constant Tg of ∼70°C, the reaction rate increased as the pH increased. Conclusion. The overall solid-state chemical reactivity of amorphous quinapril depends on the relative amount of QHCl and Q+−, the zwitterionic form of quinapril. At high proportions of Q+− (higher pH values) the reaction rate seems to be strongly influenced by the Tg of the mixture, and hence the molecular mobility, whereas at higher proportions of QHCl (lower pH) the reaction rate is less sensitive to Tg, presumably because of different mechanistic rate determining steps for the two sets of conditions. [ABSTRACT FROM AUTHOR]

Experimental studies have demonstrated that vascular injury resulted in an induction of vascular angiotensin-converting enzyme (ACE), and have suggested that inhibition of vascular ACE might be important in the prevention of restenosis. The present study aimed to determine the effect of quinapril, an ACE inhibitor with high affinity to tissue ACE, on restenosis following coronary intervention. The design of this study was a prospective, randomized, open, and non-placebo controlled trial. Patients with ischemic heart disease were enrolled after successful percutaneous transluminal coronary angioplasty or stent implantation at 7 participating institutions. Two hundred and fifty-three patients with 294 lesions were randomly assigned to the quinapril (10–20 mg per day) group or control group. Administration of quinapril was continued for 3–6 months of the follow-up. Quantitative coronary angiography was performed before and after angioplasty and at follow-up. Core laboratory measurements were performed independently and blinded. Follow-up angiography was performed in 108 patients with 124 lesions in the quinapril group and in 107 patients with 130 lesions in the control group. The baseline characteristics and findings of angioplasty showed no significant differences between the two groups. However, in the quinapril group, restenosis per patient and per lesion was significantly lower (34.3% vs. 47.7%, p < 0.05 and 30.6% vs. 43.8%, p < 0.05). Multivariable analysis revealed that administration of quinapril independently contributed to reducing the restenosis per patient and per lesion (odds ratio, 0.73; 95% confidence interval, 0.54–0.99 and odds ratio, 0.75; 95% confidence interval, 0.57–0.99). In conclusion, quinapril significantly reduces restenosis following coronary intervention. [ABSTRACT FROM AUTHOR]

Objective: We assessed the efficacy and safety of quinapril 40mg once daily for treating essential hypertension in patients with poorly controlled hypertension who were using other angiotensin-converting enzyme (ACE) inhibitors, or in those who needed to take more than one tablet a day of the ACE inhibitor to lower blood pressure, or in those who needed to start antihypertensive therapy with maximum doses of other drugs because of the severity of hypertension. Design: Prospective, observational, noncomparative, open-label. Methods: A total of 6082 patients of both genders, aged ≥40 years, received a single daily oral dose of quinapril 40mg for a period of 8 weeks. The primary end-point parameter of efficacy was the percentage of patients with adequate control of blood pressure, which was defined as systolic blood pressure (SBP) ≤140mm Hg and diastolic blood pressure (DBP) ≤90mm Hg. For the diabetic group the definition was 130/85mm Hg. Tolerability and safety of antihypertensive drugs was assessed by physical examination and detection of adverse effects potentially related to antihypertensive medication. Results: At the end of the 8-week treatment period with quinapril, adequate control of DBP, SBP and both was found in 90, 56 and 54% of patients, respectively, with a mean difference of 25mm Hg for SBP and of 15mm Hg for DBP as compared with baseline. In hypertensive patients with diabetes mellitus (n = 1269) and in patients previously treated with other ACE inhibitors (n = 2083), quinapril therapy was also associated with statistically significant decreases in mean DBP and SBP (p < 0.0001). A total of 42 adverse events were recorded. No patient failed to complete the study because of adverse events. Conclusions: Quinapril 40mg significantly lowered blood pressure, achieving adequate control of DBP in up to 90% of patients with moderate essential hypertension previously unsuccessfully controlled. [ABSTRACT FROM AUTHOR]

Purpose. To examine the mechanism of inhibition of glycylsarcosine(GlySar) transport by quinapril and enalapril, and whether or notangiotensin converting enzyme (ACE) inhibitors are transported by PEPT2as well as by PEPT1. Methods. Xenopus laevis oocytes were cRNA-injected with rat PEPT1or PEPT2 and the transport kinetics of radiolabeled GlySar were studiedin the absence and presence of quinapril and enalapril. Thetwo-microelectrode voltage-clamp technique was also performed to probe theelectrogenic uptake of captopril, quinapril and enalapril. Results. Kinetic analyses demonstrated that quinapril inhibited theuptake of GlySar in a noncompetitive manner in Xenopus oocytesinjected with PEPT1 or PEPT2 (Ki = 0.8 or 0.4 mM, respectively).In contrast, a competitive interaction was observed between GlySarand enalapril (Ki = 10.8 mM for PEPT1 or 4.3 mM for PEPT2).Most significantly, captopril and enalapril, but not quinapril, inducedinwardly-directed currents in both PEPT1- and PEPT2-expressedoocytes. Conclusions. These results are unique in providing direct evidence forthe substrate recognition and transport of some ACE inhibitors by thehigh- and low-affinity oligopeptide transporters. Our findings point todifferences between PEPT1 and PEPT2 in their affinity to, rather thanin their specificity for, ACE inhibitors. [ABSTRACT FROM AUTHOR]

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Purpose. To determine the transport mechanisms of quinapril and cephalexin in Caco-2 cell monolayers, a cell culture model of the human small intestinal epithelium. Methods. Uptake, transepithelial transport and intracellular accumulations of these two drugs were measured using Caco-2 cell monolayers grown onto Millicells and magnetically stirred diffusion chambers. Results. Transepithelial transport, apical (AP) uptake and intracellular accumulation of both drugs depended on the maintenance of a transepithelial proton gradient and temperature of the medium. However, quinapril transport and accumulation, which did not display a maximum at approximately pH 6, was more sensitive to proton gradient change, whereas cephalexin transport was more sensitive to concentration change (range 0.5-5 mM). In addition, quinapril (1 mM) transport was decreased significantly (p<0.05) by 10 mM cephalexin, loracarbef, Gly-Pro and Phe-Pro, but not by enalapril; whereas cephalexin (0.1 mM) transport was decreased significantly (p<0.05) by all four compounds. Similarly, AP quinapril (1 mM) uptake was also decreased by 10 mM loracarbef, Gly-Pro, cephalexin, and enalapril, but these inhibitory effects (20-50%) were quantitatively less than their inhibitory effects on cephalexin uptake (50-90%). Finally, the AP uptake of quinapril was also significantly (p<0.05) inhibited by FCCP (10 µg/ml), amiloride (0.5 mM), DEP (0.5 mM), and staurosporine (5 nM). Conclusions. The transport of quinapril in the Caco-2 cells is via a combination of the carrier-mediated proton gradient-dependent peptide transporter and passive diffusion. [ABSTRACT FROM AUTHOR]

Different ACE inhibitors can be distinguished in vitro by their affinity for converting enzyme in vascular and other tissues. Quinapril appears to be amongst the more effective inhibitors of vascular tissue ACE in vitro. This study assesses the in vivo effect of single oral doses of quinapril and enalapril, in attenuating the vasoconstrictive action of angiotensin I (AI) (which we have previously shown depends on its conversion to angiotensin II (AII) by vascular ACE) in the forearm resistance vessels of man. The design was of randomized, open, placebo controlled, two way crossover type, Forearm blood flow (FABF) was measured simultaneously in both forearms by mercury in silastic strain gauge plethysmography. AI infusions were via a fine bore cannula in the left brachial artery with the right arm serving as a control. Mean plasma ACE on placebo was 34.3 U·l-1. Both quinapril and enalapril produced a similar degree of plasma ACE inhibition reducing concentrations to 2.8 U·l-1 and 2.6 U·l-1 respectively. Quinapril caused a significantly greater inhibition of AI induced vasoconstriction with a 30.0% reduction compared with 67.0% and 85.0% for enalapril and placebo respectively. Enalapril attenuated AI induced vasoconstriction to a greater degree than placebo but the difference was not significantly different. These results indicate that when quinapril and enalapril are administered as single 20 mg doses, each of which produces the same degree of plasma ACE inhibition and blood pressure reduction- quinapril inhibits vascular ACE to a greater degree than both enalapril and placebo. [ABSTRACT FROM AUTHOR]

The aim of the study was to examine the effect of chronic angiotensin converting enzyme inhibition on haemodynamics and left ventricular performance during long-lasting exercise at the anaerobic threshold. For this purpose exercise haemodynamics and left ventricular performance were assessed in 14 physically trained hypertensives (aged 26 y) before and after 3 months on quinapril 20 mg once daily. During exercise intraarterial blood pressure was monitored using the Oxford method and left ventricular dimensions were measured by M-mode echocardiography. Quinapril significantly decreased mean blood pressure during the initial incremental phase of the exercise protocol and caused a slight, nonsignificant decline during the steady-state phase. The drug-induced fall in blood pressure was accounted for mainly by change in cardiac output. Exercise duration and left ventricular performance were not affected by treatment. In conclusion, quinapril 20 mg once daily smoothed the blood pressure increase which occurs during the initial phase of vigorous endurance exercise. This result was achieved without affecting physical performance or left ventricular contractility. [ABSTRACT FROM AUTHOR]

The effects of single oral doses of the angiotensin converting enzyme (ACE) inhibitor quinapril (CI-906) 40 mg and the cardioselective β-adrenoceptor blocker atenolol 100 mg on sympathetic and parasympathetic function and on exercise capacity have been studied in 8 healthy young men. The trial followed a double-blind, placebo controlled, randomized cross-over design, with at least one week between treatments. Blood pressure (BP) and heart rate (HR) at rest were slightly reduced by atenolol but were not affected by quinapril. Atenolol impaired the sympathetically mediated increases in HR and BP caused by standing, immersion of the hand into melting ice, the Valsalva manoeuvre and isometric forearm exercise. Quinapril did not influence those responses nor the vagally mediated bradycardia of the diving reflex. Atenolol, however, augmented the vagal bradycardia, presumably by sympathetic inhibition. In a dynamic bicycle ergometer test with a stepwise increasing work load, exercise performance was decreased by atenolol but not by quinapril. Inhibition of the renin-angiotensin system by quinapril was shown by a marked decrease in serum ACE activity and a several-fold increase in plasma renin activity (PRA). Atenolol produced a moderate reduction in PRA. Before or during exercise, plasma noradrenaline and adrenaline were not influenced by either drug. The results indicate that, unlike the atenolol-induced β-adrenoceptor blockade, ACE inhibition by a single dose of quinapril had no clear effect on autonomic nervous function or exercise capacity. [ABSTRACT FROM AUTHOR]

This study investigates the acute haemodynamic effects of Quinapril (CI-906) a new non-sulphydryl angiotensin converting enzyme inhibitor in 15 patients with refractory congestive cardiac failure. There were 14 males and 1 female mean age 59.5 years. After administration of Quinapril there was a significant reduction in mean arterial pressure (MAP) from 93.1 to 79 mmHg, systemic vascular resistance (SVR) from 1887 to 1349 dyn s cm and PCW from 27.3 to 15.3 mmHg. This was accompanied by an increase in CO from 3.7 to 4.7 l/min, cardiac index (CI) from 1.97 to 2.5 l/min/m and Stroke volume index from 21.1 to 28.7 ml/m. There was no significant change in heart rate (HR), right atrial pressure (RAP), or pulmonary vascular resistance. The peak effect on pulmonary capillary wedge pressure (PCW) and cardiac output (CO) occurred at 75-120 min after Quinapril administration. The maximum effect on mean arterial pressure (MAP) occurred slightly later at 120-150 min. SVR and CI exhibited 2 periods of peak effects, at 90 and 180 min. This time course is very similar to that observed in studies on the acute effects of Captopril. The significant improvement in haemodynamic measurements acutely, following administration of Quinapril 5 mg orally, suggests that this drug is worthy of further study in the management of patients with refractory congestive cardiac failure, in particular its long term effects. [ABSTRACT FROM AUTHOR]

The mechanism of quinapril's interaction with the organic anion transporter was characterized by studying its effect on the transport of p -aminohippurate (PAH) in rabbit renal basolateral membrane vesicles (BLMV). Cis-inhibition studies demonstrated that quinapril was a specific and potent inhibitor of PAH. The Ki of quinapril was about 20 μM, a value similar to that of probenecid and eight-times lower than the Km value of 165 μM for PAH. Even though quinapril resulted in trans-inhibition of PAH uptake during counterflow studies, kinetic studies revealed that quinapril was a competitive inhibitor of PAH transport. This latter finding suggests that quinapril and PAH share a common binding site on the transporter. Overall, the results indicate that quinapril is a high-affinity inhibitor of the organic anion transporter in renal BLMV, and that drug–drug interactions may occur with other organic anions at the basolateral membrane of proximal cells. [ABSTRACT FROM AUTHOR]

Gliddon et al. conducted a randomized, double-blind, multicenter, placebo-controlled study to evaluate the efficacy of the angiotensin-converting enzyme inhibitor quinapril for the management of vascular damage in systemic sclerosis (SSc). The trial comprised 213 patients with limited cutaneous SSc or Raynaud's phenomenon (mean age 54 years, 182 females) who were randomly assigned to receive 80 mg/day, or the maximum tolerated dose, of quinapril (n = 105) or placebo (n = 108) for 2-3 years. Patients were assessed every 3 months. The number of new ischemic digital ulcers was recorded as the primary end point, while the frequency of Raynaud's phenomenon episodes, skin score, health status, pulmonary artery pressure and treatments for ischemia were also monitored as secondary end points. There were no detectable differences between patients treated with quinapril and those receiving placebo; however, although no severe adverse effects were observed, patients taking quinapril experienced significantly more adverse effects. [ABSTRACT FROM AUTHOR]

Deals with a study that determined whether quinapril would result in greater hypertension control rates and fewer adverse effects in patients with stages one and two hypertension when dose escalation was undertaken at a slower pace. Methodology; Results; Conclusion.

The pharmacokinetics and pharmacodynamics of the ACE inhibitor quinaprilat have been studied in six chronic haemodialysis (HD) patients and in six patients undergoing continuous ambulatory peritoneal dialysis (CAPD) after a single oral dose of 2.5 mg quinapril. Mean t and C values (SEM) for quinaprilat in interdialytic HD patients were 4.0 (0) h and 84 (8.4) ng · ml respectively, and they did not differ significantly from those in CAPD patients (4.7 (0.7) h and 64 (5.7) ng · ml). Elimination half lives were 30 (10.1) h (HD) and 34 (7.3) h (CAPD). C, t, t, and AUC were increased and CL was decreased compared to data reported previously after giving 2.5 mg to healthy subjects. Peritoneal clearance was calculated as 0.1 (0.1) ml · min, thus less than 0.5 % of the dose were removed within 24 h by CAPD. ACE activity was suppressed by more than 93 % between 4 and 24 h postdose ( P < 0.001). It decreased in both groups with increasing plasma quinaprilat levels. Angiotensin II concentration compared to baseline was significantly decreased at 4 hours (−30.4±10 %) and 24 h (−30±9.9 %) ( P < 0.05, n=11), while active plasma renin concentration was still significantly increased at 48 h postdose (+60.2±14.5 %, P < 0.01). Mean arterial pressure 24 h postdose was significantly ( P < 0.05) decreased in HD (−12 mm Hg) and CAPD patients (− 20 mm Hg). Only two patients reported unwanted effects (fatigue, dizziness, nausea, and weakness). In conclusion, due to its long lasting effect on ACE activity and on blood pressure in terminal renal failure a starting dose of quinapril 2.5 mg o. d. may be used in hypertensive HD and CAPD patients. [ABSTRACT FROM AUTHOR]