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Ilkka Pörsti - One of the best experts on this subject based on the ideXlab platform.
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Endothelial function in spontaneously hypertensive rats: influence of Quinapril treatment.
British journal of pharmacology, 1995Co-Authors: Mika Kähönen, Pertti Arvola, Heikki Mäkynen, Ilkka PörstiAbstract:Abstract 1. Angiotensin converting enzyme (ACE) inhibition has been shown to restore the impaired endothelial function in hypertension, but the mediators underlying the promoted endothelium-dependent dilatation have not been fully characterized. Therefore, we investigated the effects of 10-week-long Quinapril therapy (10 mg kg-1 day-1) on responses of mesenteric arterial rings in vitro from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. 2. Endothelium-dependent relaxations of noradrenaline (NA)-precontracted rings to acetylcholine (ACh) and adenosine 5'-diphosphate (ADP) were similar in WKY rats and Quinapril-treated SHR and more pronounced than in untreated SHR. The nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) attenuated the relaxations in both WKY groups and Quinapril-treated SHR, and completely inhibited them in untreated SHR. When endothelium-dependent hyperpolarization was prevented by precontraction of the preparations with potassium chloride (KCl), no differences were found in relaxations to ACh and ADP between the study groups. In addition, in NA-precontracted rings the L-NAME- and indomethacin-resistant relaxations to ACh were partially prevented by apamin, an inhibitor of calcium-activated potassium channels. 3. Interestingly, in Quinapril-treated SHR but not in the other groups, exogenous bradykinin potentiated the relaxations to ACh in both NA- and KCl-precontracted arterial rings. 4. Contractile sensitivity of endothelium-intact rings to NA was reduced in SHR by Quinapril, and was more effectively increased by L-NAME in Quinapril-treated than untreated SHR.(ABSTRACT TRUNCATED AT 250 WORDS)
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Quinapril treatment and arterial smooth muscle responses in spontaneously hypertensive rats
British journal of pharmacology, 1993Co-Authors: Pertti Arvola, Heikki Ruskoaho, Heikki Wuorela, Anu Pekki, Heikki Vapaatalo, Ilkka PörstiAbstract:1 The effects of long-term angiotensin-converting enzyme inhibition with Quinapril on arterial function were studied in spontaneously hypertensive rats, Wistar-Kyoto rats serving as normotensive controls. 2 Adult hypertensive animals were treated with Quinapril (10 mg kg-1 day-1) for 15 weeks, which reduced their blood pressure and the concentrations of atrial natriuretic peptide in plasma and ventricular tissue to a level comparable with that in normotensive rats. 3 Responses of mesenteric arterial rings in vitro were examined at the end of the study. Compared with normotensive and untreated hypertensive rats, responses to noradrenaline were attenuated in hypertensive animals on Quinapril, both force of contraction and sensitivity being reduced. Quinapril also attenuated maximal contractions but not sensitivity to potassium chloride. Nifedipine less effectively inhibited vascular contractions in normotensive and Quinapril-treated than in untreated hypertensive rats. 4 Arterial relaxation responses by endothelium-dependent (acetylcholine) and endothelium-independent (sodium nitrite, isoprenaline) mechanisms were similar in normotensive and Quinapril-treated rats and more pronounced than in untreated hypertensive rats. 5 Cell membrane permeability to ions was evaluated by means of potassium-free solution-induced contractions of endothelium-denuded denervated arterial rings. These responses were comparable in normotensive and Quinapril-treated rats and less marked than in untreated hypertensive rats. 6 Intracellular free calcium concentrations in platelets and lymphocytes, measured by the fluorescent indicator quin-2, were similar in normotensive and Quinapril-treated rats and lower than in untreated hypertensive rats. 7 In conclusion, Quinapril treatment improved relaxation responses and attenuated contractions in arterial smooth muscle of hypertensive rats. These changes may be explained by diminished cytosolic free calcium concentration, reduced cell membrane permeability, and alterations in dihydropyridine-sensitive calcium channels following long-term angiotensin-converting enzyme inhibition.
William H. Frishman - One of the best experts on this subject based on the ideXlab platform.
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The efficacy and safety of Quinapril in the treatment of moderate to severe and severe hypertension: Comparison to captopril
Clinical Cardiology, 2009Co-Authors: William H. FrishmanAbstract:Major studies comparing the efficacy and safety of Quinapril and captopril in the treatment of moderate to severe or severe hypertension are reviewed. Given concurrently with hydrochlorothiazide 25 mg/day to patients with moderate to severe hypertension, Quinapril 20-80 mg/day twice daily was found to be more effective than captopril 50-200 mg/day twice daily, and Quinapril 10-40 mg/day once daily was found to be as effective as captopril 25-100 mg/day twice daily. Given as initial monotherapy to patients with severe hypertension, Quinapril 10-40 mg/day twice daily was found to be as effective as captopril 50-200 mg/day twice daily. Quinapril was found to be well tolerated, both when administered against a diuretic background and when diuretic was added to a Quinapril regimen.
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The safety and efficacy of Quinapril in the treatment of mild to moderate essential hypertension.
Clinical Cardiology, 2009Co-Authors: William H. FrishmanAbstract:Major clinical trials are reviewed comparing the efficacy and safety of Quinapril hydrochloride, a new nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor, with that of placebo, captopril, and enalapril in the treatment of mild to moderate essential hypertension. A randomized, double-blind 12-week study of 270 patients compared the efficacy of placebo with once or twice daily doses of Quinapril (20, 40, 80 mg/day, with forced titration). Quinapril effectively lowered both diastolic blood pressure (DBP) and systolic blood pressure. Mean reductions in DBP of up to 13 mmHg from baseline were obtained. At full dosage, more than 65% of patients achieved a clinically significant reduction in DBP. Quinapril was similarly effective whether the total daily dose was given once or twice daily. In a multicenter, double-blind study involving more than 400 patients, the efficacy of Quinapril (10-40 mg/day, given once or twice daily) was found to be similar to captopril (25 mg bid to 50 mg tid). Hydrochlorothiazide (HCTZ) safely provided additive effects when given to nonresponders in both treatment groups. In a 28-week double-blind study of 258 patients comparing the efficacy of Quinapril or enalapril at doses of 10, 20, and 40 mg/day (with optional titration), Quinapril was found to be of similar efficacy as enalapril. The large majority of patients on either regimen were controlled with monotherapy. HCTZ again safely provided additive effects. Quinapril was well tolerated in all trials, with the incidence of adverse events and withdrawals tending to be lower with Quinapril than with enalapril or captopril.
R.m. Jiménez - One of the best experts on this subject based on the ideXlab platform.
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determination of the angiotensin converting enzyme inhibitor Quinapril and its metabolite Quinaprilat in pharmaceuticals and urine by capillary zone electrophoresis and solid phase extraction
Electrophoresis, 2002Co-Authors: J.a Prieto, Rosa M. Alonso, R.m. JiménezAbstract:Quinapril is an antihypertensive drug commonly used in the treatment of hypertension and congestive heart failure. In this work, a capillary zone electrophoresis system is optimized for the analysis of Quinapril and its active metabolite Quinaprilat in urine, as well as for the determination of the drug and its combination with hydrochlorothiazide in pharmaceuticals. The separation takes place in a fused-silica capillary. The running electrolyte consists of a 60 mM borate buffer solution, pH 9.5. The analysis of urine samples requires a previous extraction step using C8 solid-phase cartridges. Under the optimum experimental conditions, the separation of the two analytes and the internal standard takes less than 5 min. The detection limits obtained (75 and 95 ng/mL for Quinapril and Quinaprilat, respectively) allow the application of the electrophoretic method to the determination of the drug and its metabolite in urine samples obtained from four patients treated with Quinapril.
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Solid-phase extraction and high-performance liquid chromatography applied to the determination of Quinapril and its metabolite Quinaprilat in urine.
Journal of chromatographic science, 2001Co-Authors: J.a Prieto, Rosa M. Alonso, R.m. Jiménez, A. BlancoAbstract:Quinapril is an antihypertensive drug that belongs to the family of angiotensin-converting enzyme inhibitors. It is metabolized to Quinaprilat, which is the compound that is really responsible for the therapeutic action. In this study, a rapid and simple liquid chromatographic method with photometric detection is described and applied to the determination of Quinapril and Quinaprilat in urine. The cleanup procedure for the urine samples consists of a solid-liquid extraction using C8 cartridges. Under these conditions, both compounds and the internal standard (enalapril maleate) are separated in less than 9 min. Recoveries for Quinapril and Quinaprilat are greater than 80%. The method is sensitive enough (detection limit of 60 ng/mL for Quinapril and 50 ng/mL for Quinaprilat) to be applied for the determination of Quinapril and Quinaprilat in urine samples obtained from four hypertensive patients after the intake of a therapeutic dose.
David E. Smith - One of the best experts on this subject based on the ideXlab platform.
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noncompetitive inhibition of glycylsarcosine transport by Quinapril in rabbit renal brush border membrane vesicles effect on high affinity peptide transporter
Journal of Pharmacology and Experimental Therapeutics, 1998Co-Authors: Wiyada Akarawut, Chunjung Lin, David E. SmithAbstract:Angiotensin converting enzyme (ACE) inhibitors are important therapeutic agents for treating patients with hypertension and cardiovascular diseases. Although most ACE inhibitors are cleared by the kidney via glomerular filtration and tubular secretion, little is known about their reabsorption potential. In particular, it is believed that while certain ACE inhibitors are transported by the intestinal peptide transporter (PepT1), these same compounds do not interact with the renal peptide transporter (PepT2). In the present study, we examined the interaction of Quinapril with the high-affinity peptide transporter, PepT2. Studies were performed in rabbit renal brush border membrane vesicles in which the uptake of [14C]glycylsarcosine (GlySar), at low substrate concentrations, was examined in the absence and presence of Quinapril (and other ACE inhibitors). We found that Quinapril was capable of cis-inhibiting the uptake of GlySar and in a concentration-dependent manner. While the Ki for Quinapril ( approximately 1 mM) was several-fold higher than the Km for GlySar ( approximately 160 microM), the interaction was unique in that inhibition of PepT2 was of a noncompetitive type. Overall, the data suggest that Quinapril is a low-affinity inhibitor of the renal peptide transporter and that it binds to a site distinct from that of the GlySar binding site.
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Competitive Inhibition of p-Aminohippurate Transport by Quinapril in Rabbit Renal Basolateral Membrane Vesicles
Journal of pharmacokinetics and biopharmaceutics, 1998Co-Authors: Wiyada Akarawut, David E. SmithAbstract: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 Kiof Quinapril was about 20 μM, a value similar to that of probenecid and eight-times lower than the Kmvalue 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.
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Disposition of Quinapril and Quinaprilat in the isolated perfused rat kidney
Journal of pharmacokinetics and biopharmaceutics, 1995Co-Authors: Alan R. Kugler, Stephen C. Olson, David E. SmithAbstract:An isolated perfused rat kidney model was used to probe the renal disposition of Quinapril and Quinaprilat after separate administration of each drug species. Control studies were performed with drug-free perfusate (n=8) and perfusate containing Quinapril (n=9) Quinaprilat (n=7) at initial drug concentrations of 1000 ng/ml (including corresponding tracer levels of tritiated drug). Physiologic parameters were within the normal range of values for this technique and were stable for the duration of each experiment. Quinapril and Quinaprilat concentrations were determined in perfusate, urine, and perfusate ultrafiltrate using a specific and sensitive reversed-phase HPLC procedure with radiochemical detection, coupled to liquid scintillation spectrometry. Perfusate protein binding was determined using an ultrafiltration method at 37°C. The total renal learance of Quinapril (CLr) was calculated asDose/AUC (0-∞), and is represented by the sum of its urinary and metabolic clearances. The urinary clearances (CLe) of Quinapril and Quinaprilat were calculated as urinary excretion rate divided by midpoint perfusate concentration for each respective species. Of the total renal clearance for Quinapril (CLr=4.49 ml/min), less than 0.1% was cleared as unchanged drug (CLe=0.004 ml/min); over 99% of the drug was cleared as Quinaprilat formed in the kidney. The clearance ratio of Quinapril [CR=CLr/(fu·GFR)] was 41.0, a value representing extensive tubular secretion into the renal cells. Following Quinaprilat administration, the clearance ratio of metabolite [CR=CLe/(fu β GFR)] was 3.85, indicating a net secretion process for renal elimination.
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determination of Quinapril and Quinaprilat by high performance liquid chromatography with radiochemical detection coupled to liquid scintillation counting spectrometry
Journal of Chromatography B: Biomedical Sciences and Applications, 1995Co-Authors: Stephen C. Olson, Alan R. Kugler, David E. SmithAbstract:Quinapril and Quinaprilat concentrations were determined in perfusate, urine, and perfusate ultrafiltrate using a specific and sensitive reversed-phase high-performance liquid chromatographic procedure with radiochemical detection, coupled to liquid scintillation counting spectrometry. Quinapril and Quinaprilat were measured in perfusate and urine after pretreatment with acetonitrile and subsequent centrifugation. Perfusate ultrafiltrate was used as collected. Two Quinapril diketopiperazine metabolites, PD 109488 and PD 113413, were separated chromatographically from Quinapril, Quinaprilat, and from each other. Assay performance for Quinapril and Quinaprilat was assessed by examining precision and accuracy of the assay over four days. Using a 100-μl sample volume, the limit of quantitation for both 3H-Quinapril and 3H-Quinaprilat (sp. act. ≈ 2.0 μCi/μg) was 1 ng/ml.
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Reabsorption and Metabolism of Quinapril and Quinaprilat in Rat Kidney: In Vivo Micropuncture Studies
Journal of pharmaceutical sciences, 1995Co-Authors: David E. Smith, Alan R. Kugler, Jurgen SchnermannAbstract:Abstract The tubular uptake and esterolysis of Quinapril and Quinaprilat were studied in male Sprague‐Dawley rats using an in vivo micropuncture technique. [ 3 H]Quinapril or [ 3 H]Quinaprilat was injected with [ 14 C]inulin into either proximal or distal segments of the renal tubules, and urine was collected over 30 min. Urine and perfusate were assayed for [ 14 C]inulin using dual label spectrometry. [ 3 H]Quinapril and [ 3 H]Quinaprilat concentrations were determined in urine and perfusate using a reversed‐phase HPLC procedure with radiochemical detection, coupled to liquid scintillation spectrometry. These studies demonstrated that Quinapril could access the esterase enzyme from tubular fluid and be metabolized to Quinaprilat in both proximal and to a lesser extent distal segments of the kidney tubule. Quinapril, but not Quinaprilat, was extensively reabsorbed. Its reabsorption along the proximal tubule and/or the loop of Henle could account for as much as 45–50% of the available dose of Quinapril. Further, the urinary recovery of Quinapril and Quinaprilat (after dosing Quinapril into proximal segments) was urine flow rate dependent.
Michihide Setoguchi - One of the best experts on this subject based on the ideXlab platform.
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Prolonged inhibition of local angiotensin-converting enzyme after single or repeated treatment with Quinapril in spontaneously hypertensive rats.
Journal of cardiovascular pharmacology, 1992Co-Authors: Tohru Nakajima, Tsuneyo Yamada, Michihide SetoguchiAbstract:Plasma and tissue angiotensin-converting enzyme (ACE) activities were measured in spontaneously hypertensive rats (SHR) after single or repeated oral (p.o.) treatment with a hypotensive dose (1 mg/kg) of Quinapril and compared with those after administration of enalapril (1 mg/kg). The degree of ACE inhibition in response to Quinapril varied in tissues; marked inhibition was observed in aorta, lung, and plasma by single treatment with Quinapril, and inhibition in plasma and aorta caused by Quinapril was more potent than that caused by enalapril. The prolonged ACE inhibition was observed in the aorta, a target organ, by repeated treatment with Quinapril for 2 weeks. These results indicate that Quinapril has a good pharmacokinetic profile, namely rapid absorption and easy penetration to the target organ. In addition, Quinapril produced greater inhibition of cardiac ACE than did enalapril after either p.o. or intravenous (i.v.) administration, suggesting the beneficial effects of Quinapril in treatment of congestive heart failure (CHF).
