Angiotensin-converting enzyme inhibitors (ACE inhibitors) such as quinapril (HCl) (CI-906) are used to treat congestive heart failure and hypertension. Following absorption, quinapril quickly deesterifies to form quinapril, an effective inhibitor of the angiotensin-converting enzyme (ACE) [1][2].

Absorption, Distribution and Excretion
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/

---

Metabolism / Metabolites
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 ... .

---

Biological Half-Life
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/

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Because of the low levels of quinapril in breastmilk, amounts ingested by the infant are small and would not be expected to cause any adverse effects in breastfed infants.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

---

Interactions
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.

---

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

[1]. Song, J.C. and C.M. White, Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors: an update. Clin Pharmacokinet, 2002. 41(3): p. 207-24.

[2]. Culy, C.R. and B. Jarvis, Quinapril: a further update of its pharmacology and therapeutic use in cardiovascular disorders. Drugs, 2002. 62(2): p. 339-85.

Quinapril hydrochloride is a hydrochloride resulting from the reaction of equimolar amounts of quinapril and hydrogen chloride. A prodrug for quinaprilat hydrochloride (by hydrolysis of the ethyl ester to the corresponding carboxylic acid), it is used as an angiotensin-converting enzyme inhibitor (ACE inhibitor) for the treatment of hypertension and congestive heart failure. It has a role as an antihypertensive agent and an EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor. It contains a quinapril(1+).
Quinapril Hydrochloride is the hydrochloride salt form of quinapril, a prodrug and non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor with antihypertensive activity. Quinapril is hydrolized into its active form quinaprilat, which binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This abolishes the potent vasoconstrictive actions of angiotensin II and leads to vasodilatation. Quinapril also causes a decrease in angiotensin II-induced aldosterone secretion by the adrenal cortex, thereby promoting diuresis and natriuresis, and increases bradykinin levels.
A tetrahydroisoquinoline derivative and ANGIOTENSIN CONVERTING ENZYME inhibitor that is used in the treatment of HYPERTENSION and HEART FAILURE.
See also: Quinapril (has active moiety); Quinaprilat (has active moiety); Hydrochlorothiazide; quinapril hydrochloride (component of).

---

Mechanism of Action
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/

---

Therapeutic Uses
... /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.

---

Drug Warnings
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.

C25H30N2O5.HCL

474.98

474.192

82586-55-8

Quinapril-d5;1279029-79-6

54891

White to off-white solid powder

662ºC at 760 mmHg

120-130ºC

354.1ºC

3.697

3

6

10

33

648

3

CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@@H](C)C(=O)N2CC3=CC=CC=C3C[C@H]2C(=O)O.Cl

IBBLRJGOOANPTQ-JKVLGAQCSA-N

InChI=1S/C25H30N2O5.ClH/c1-3-32-25(31)21(14-13-18-9-5-4-6-10-18)26-17(2)23(28)27-16-20-12-8-7-11-19(20)15-22(27)24(29)30;/h4-12,17,21-22,26H,3,13-16H2,1-2H3,(H,29,30);1H/t17-,21-,22-;/m0./s1

(3S)-2-[(2S)-2-[[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]propanoyl]-3,4-dihydro-1H-isoquinoline-3-carboxylic acid;hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.26 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (5.26 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (5.26 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

Solubility in Formulation 4: 100 mg/mL (210.54 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C).

---

 (Please use freshly prepared in vivo formulations for optimal results.)