Quinapril hydrochloride

474.98

474.192139

1308068-626-2

33067B3N2M

758222

DTXSID3021221

C29398

2933492250

95.9

3.69790

white

120-130 °C

662°C at 760 mmHg

354.1ºC

H2O: >10mg/mL

2-8°C

Freely sol in aq solvents. LD50 in male, female mice, rats (mg/kg): 1739, 1840, 4280, 3541 orally; 504, 523, 158, 107 i.v. (Kaplan, 1989)

D23 +14.5° (c = 1.2 in ethanol) (Klutchko); D25 +15.4° (c = 2 in methanol) (Goel, Krolls)

203.5 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Crystals from ethyl acetate-toluene ... /with/ specific optical rotation at 23 °C for D (sodium) line = +14.5 deg (c = 1.2 in ethanol). Also reported as white crystalline solid from acetonitrile ... /with/ specific optical rotation at 25 °C for D (sodium) line = +15.4 deg (c = 2 in methanol).|White to off-white amorphous powder that is freely soluble in aqueous solvents

NONH for all modes of transport

2

22-24/25

NW7176000

P201, P202, P281, P308+P313, P405, P501

H361

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl quinapril hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

|Warning|H361 (98.4%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]|P201, P202, P281, P308+P313, P405, and P501|Aggregated GHS information provided by 125 companies from 6 notifications to the ECHA C&L Inventory.

Quinapril, like other ACE inhibitors, has been associated with a low rate of serum aminotransferase elevations (

Hyperkalemia may occur with potassium supplements, potassium-sparing agents, & NSAIDs. /ACE inhibitors; from table/ /Salt not specified/|... ACE inhibitors enhance the efficacy of diuretic drugs. This means that even very small doses of diuretics may substantially improve the antihypertensive efficacy of ACE inhibitors; & on the other end of the spectrum, the use of high doses of diuretics together with angiotensin converting enzyme inhibitors may lead to excessive reduction in blood pressure & to /sodium ion/ loss in some patients. /ACE inhibitors/ /Salt not specified/|Oligopeptidic drugs such as beta-lactams & angiotensin-converting enzyme inhibitors share the same carriers in humans & animals, which results in possible pharmacokinetic interactions. To model such interactions, the effects of quinapril on cephalexin pharmacokinetics were investigated in rats. Blood cephalexin concns were measured by liquid chromatography, & the data were analyzed by a noncompartmental method & by fitting a bicompartmental model by a nonlinear mixed-effect modeling approach. 5 groups of 8 rats were examined. In the first 3 groups, cephalexin elimination kinetics after intra-arterial admin alone or in combination with quinapril given by the parenteral or the oral route were studied, & the occurrence of a pharmacokinetic interaction was not revealed. The absence of an effect of quinapril on cephalexin elimination after parenteral admin 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 concns of cephalexin than those of quinapril. In the last 2 groups, cephalexin was administered by the oral route alone or in combination with quinapril. The mean area under the concn-time curve (AUC) for cephalexin was increased by ca. 30% by coadmin of quinapril (40.1 versus 31.4 mg.hr/liter; P=0.04). The mean elimination clearance of cephalexin was significantly decreased by quinapril, from 0.81 to 0.64 liter/hr/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 hr-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. /Salt not specified/|Concurrent use /of other hypotension-producing medications/ with ACE inhibitors may produce additive hypotensive effects. /ACE inhibitors/ /Salt not specified/|For more Interactions (Complete) data for QUINAPRIL HYDROCHLORIDE (16 total), please visit the HSDB record page.

LD50 in male, female mice, rats (mg/kg): 1739, 1840, 4280, 3541 orally; 504, 523, 158, 107 i.v. /Salt not specified/

Quinapril is an angiotensin-converting enzyme (ACE) inhibitor used in the therapy of hypertension and congestive heart failure. Quinapril is associated with a low rate of transient serum aminotransferase elevations, but has yet to be linked to instances of acute liver injury.

Angiotensin-Converting Enzyme Inhibitors

... /Quinapril/ has proven to be very useful for the treatment of hypertension ... . /Salt not specified/|The angiotensin converting enzyme (ACE) inhibitors appear to confer a special advantage in the treatment of patients with diabetes, slowing the development of diabetic glomerulopathy. They also have been shown to be effective in slowing the progression of other forms of chronic renal disease, such as glomerulosclerosis, & many of these patients also have hypertension. An ACE inhibitor is probably the preferred initial agent in the treatment of hypertensive patients with left ventricular hypertrophy. Patients with hypertension & ischemic heart disease are candidates for treatment with ACE inhibitors; this includes treatment in the immediate post-myocardial infarction period which has been shown to lead to improved ventricular function & reduced morbidity & mortality. /ACE inhibitors/ /Salt not specified/|The combination of ... quinapril and hydrochlorothiazide is indicated in the treatment of hypertension. Fixed-dosage combinations generally are not recommended for initial therapy, but are utilized in maintenance therapy after the required dose is established in order to increase convenience, economy, and patient compliance. /Included in US product labeling/ /Salt not specified/|Angiotensin converting enzyme (ACE) inhibitor /Salt not specified/|For more Therapeutic Uses (Complete) data for QUINAPRIL HYDROCHLORIDE (6 total), please visit the HSDB record page.

Reduce dose ... in patients with serum creatinine > or =221 umol/L (2.5 mg/dL). /ACE Inhibitors; from table/ /Salt not specified/|May cause hyperkalemia in patients with renal impairment or in those receiving potassium-sparing agents. /ACE Inhibitors; from table/ /Salt not specified/|Can cause acute renal failure in patients with severe bilateral renal artery stenosis or severe stenosis in artery to solitary kidney. /ACE Inhibitors; from table/ /Salt not specified/|Conversion of quinapril to quinaprilat is reduced in patients with diminished liver function. /Salt not specified/|For more Drug Warnings (Complete) data for QUINAPRIL HYDROCHLORIDE (12 total), please visit the HSDB record page.

A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. (See all compounds classified as Angiotensin-Converting Enzyme Inhibitors.)|Agents that affect the rate or intensity of cardiac contraction, blood vessel diameter, or blood volume. (See all compounds classified as Cardiovascular Agents.)|Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS. (See all compounds classified as Antihypertensive Agents.)

Absorption (bioavailability) of quinapril is 60%; time to peak serum concn is 2 hr; half-life (elimination) is 2 hr; protein binding is 97%; metabolism is in the liver. /from table/ /Salt not specified/|Quinapril is rapidly absorbed (peak concns are achieved in 1 hr, but the peak may be delayed after food), & its rate but not extent of oral absorption (60%) may be reduced by food. Quinapril is metabolized to quinaprilat & to other minor metabolites, & quinaprilat is excreted in the urine (61%) & the feces (37%). Peak concns of quinaprilat in plasma are achieved in about 2 hr. Conversion of quinapril to quinaprilat is reduced in patients with diminished liver function. The initial half-life of quinaprilat is about 2 hr; a prolonged terminal half-life of about 25 hr may be due to high-affinity binding of the drug to tissue ACE. /Salt not specified/

Cleavage of the ester moiety by hepatic esterases transforms quinapril hydrochloride, a prodrug, into quinaprilat, an ACE inhibitor that in vitro is about as potent as benazeprilat. ... Quinapril is metabolized to quinaprilat & to other minor metabolites ... .

The initial half-life of /the metabolite/ quinaprilat is about 2 hr; a prolonged terminal half-life of about 25 hr may be due to high-affinity binding of the drug to tissue ACE. /Salt not specified/

Block formation of angiotensin II, promoting vasodilation & decreased aldosterone; also increased bradykinin & vasodilatory prostaglandins. /ACE Inhibitors; from table/ /Salt not specified/|Quinapril is deesterified to the principal metabolite, quinaprilat, which is an inhibitor of ACE activity in human subjects and animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor, angiotensin II. The effect of quinapril in hypertension and in congestive heart failure (CHF) appears to result primarily from the inhibition of circulating and tissue ACE activity, thereby reducing angiotensin II formation. Quinapril inhibits the elevation in blood pressure caused by iv administered angiotensin I, but has no effect on the pressor response to angiotensin II, norepinephrine or epinephrine. Angiotensin II also stimulates the secretion of aldosterone from the adrenal cortex, thereby facilitating renal sodium and fluid reabsorption. Reduced aldosterone secretion by quinapril may result in a small incr in serum potassium. In controlled hypertension trials, treatment with ACCUPRIL alone resulted in mean increases in potassium of 0.07 mmol/L ... . Removal of angiotensin II negative feedback on renin secretion leads to increased plasma renin activity (PRA). /Salt not specified/

... Following gut decontamination, treatment is primarily supportive to maintain an adequate blood pressure. /ACE Inhibitors/ /Salt not specified/

/HUMAN EXPOSURE STUDIES/ ACE inhibitors should be avoided in 2nd and 3rd trimesters because of severe fetal and neonatal toxicity (oligohydramnios, pulmonary hypoplasia, renal failure, anuria, death); severe, persistent, neonatal hypotension may occur. Structural defects after exposure in 2nd or 3rd trimesters include fetal calvarial hypoplasia and, possibly, renal anomalies. /ACE inhibitors; from table/ /Salt not specified/|/HUMAN EXPOSURE STUDIES/ Angioedema is an infrequent but serious and potentially fatal adverse effect of all the ACE inhibitors. Thus, patients starting treatment with these drugs should be explicitly warned to discontinue their use with the advent of any signs of angioedema. /ACE inhibitors/ /Salt not specified/|/SIGNS AND SYMPTOMS/ The principal adverse effect of ACE inhibitor overdose is hypotension, although hyperkalemia & renal failure may occur. ... /ACE inhibitors/ /Salt not specified/

2-(2-((1-(ethoxycarbonyl)-3-phenylpropyl)amino)-1-oxopropyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid

CI-906; PD-109452-2; Accupril; Accuprin; Accupro; Acequin; Acuitel; Korec; Quinazil|Quinaprilat /Diacid of Quinapril/|Acequide; Koretic /Mixture with Hydrochlorothiazide/|The main ingredient in the drug Accupril ... (tablets)

The main ingredient in the drug Accuretic ... (tablets) /Mixture with Hydrochlorothiazide/|The major objective of this study was to investigate the effects of beta-cyclodextrin (beta-CD) & hydroxypropyl-beta-cyclodextrin (HP-beta-CD) on the solid-state chemical reactivity of the drug, quinapril, when amorphous samples are prepared by colyophilization of quinapril & each of these beta-CDs. For comparison, a physical mixture with beta-CD & colyophilized mixtures with trehalose & dextran were also prepared & subjected to a similar chemical stability test at 80 °C followed by HPLC analysis. Significant inhibition of degradation was observed only for colyophilized miscible mixtures with beta-CD & HP-beta-CD at molar ratios in excess of 1:1. Colyophilized mixtures with trehalose & dextran, shown to have phase separated, & the physical mixture with beta-CD exhibited no inhibiting effects. This suggests that specific molecular complexation is responsible for the significant inhibition by the beta-CDs. The tendency of quinapril to form molecular complexes in soln with the beta-CDs was measured by (1)H solution NMR, by estimating complexation constants from the chemical shift of specific groups on quinapril. Supporting evidence for solid-state complexation was provided by FTIR analysis. DSC & TSC measurements indicated that the beta-CDs do not have high enough glass transition temperatures to reduce reactivity by reducing molecular mobility.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients