Angiotensin-converting enzyme (ACE); Quinapril HCl (CI-906) inhibited human plasma ACE with an IC50 value of approximately 1.9 nM, and its active metabolite quinaprilat inhibited human plasma ACE with an IC50 value of approximately 0.16 nM [2]

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].

---

Quinapril HCl (CI-906) exhibited dose-dependent inhibitory activity against angiotensin-converting enzyme (ACE) in vitro. In human plasma ACE assays, Quinapril HCl (CI-906) showed a weaker inhibitory effect compared to its active metabolite quinaprilat, with IC50 values of ~1.9 nM and ~0.16 nM, respectively [2]

Absorption, Distribution and Excretion
Quinapril has an absorption (bioavailability) of 60%; a peak concentration time of 2 hours; a half-life (elimination) of 2 hours; and a protein binding rate of 97%. Metabolism primarily occurs in the liver. /Excerpt from table/ /Salt content not specified/ Quinapril is rapidly absorbed (peak concentration is reached within 1 hour, but peak concentration may be delayed after food intake). Food may reduce its oral absorption rate (60%), but does not affect its overall absorption. Quinapril is metabolized into quinaprilat and other minor metabolites. Quinaprilat is primarily excreted in urine (61%) and feces (37%). Peak plasma concentrations of quinaprilat are reached approximately 2 hours later. Patients with impaired hepatic function have a reduced conversion rate of quinapril to quinaprilat. The initial half-life of quinaprilat is approximately 2 hours; its terminal half-life is prolonged to approximately 25 hours, possibly due to the drug's high affinity for tissue ACE. /Unspecified Salt/

---

Metabolism/Metabolites>
The prodrug quinapril hydrochloride is converted to quinaprilat by hepatic esterase hydrolysis, which is an ACE inhibitor with in vitro potency comparable to benazeprilat. ...Quinapril is metabolized to quinaprilat and other minor metabolites...

---

Biological Half-Life>
The initial half-life of the metabolite quinaprilat is approximately 2 hours; its terminal half-life is extended to approximately 25 hours, possibly due to the drug's high affinity for tissue ACE. /Unspecified Salt/

---

Absorption: In healthy volunteers, after oral administration of quinapril hydrochloride (CI-906) (10–80 mg), the oral bioavailability of quinapril (the parent drug) is approximately 60%, while the bioavailability of its active metabolite quinaprilat is approximately 25% (due to first-pass metabolism). Food intake reduced the peak plasma concentration (Cmax) of quinapril by about 30%, but had no significant effect on the area under the plasma concentration-time curve (AUC)[1][2]
-Distribution: The volume of distribution (Vd) of quinapril (the active metabolite) in healthy volunteers was about 0.2 L/kg. Quinapril hydrochloride (CI-906) and quinapril did not significantly cross the blood-brain barrier[2]
-Metabolism: Quinapril hydrochloride (CI-906) is rapidly metabolized in the liver via ester hydrolysis to produce its active metabolite, quinapril (the main pharmacologically active form). Small amounts of quinapril are also metabolized to inactive conjugates (e.g., glucuronide)[1][2]
-Excretion: Quinapril is mainly excreted via the kidneys and feces. In healthy volunteers, approximately 39% of the administered dose was excreted in the urine as quinapril within 24 hours, and approximately 15% was excreted in the feces. The elimination half-life (t1/2) of quinapril in healthy volunteers was approximately 2.5–3 hours; in patients with severe renal impairment (creatinine clearance <30 mL/min), the half-life of quinapril was prolonged to approximately 10 hours [1][2]

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Because quinapril is present in low amounts in breast milk, the amount ingested by the infant is very small, and no adverse effects are expected on breastfed infants.
◉ Effects on Breastfed Infants
No published information found as of the revision date.
◉ Effects on Lactation and Breast Milk
No published information found as of the revision date.

---

Drug Interactions
Hyperkalemia may occur with co-administration with potassium supplements, potassium-sparing diuretics, and nonsteroidal anti-inflammatory drugs (NSAIDs). /ACE Inhibitors; from Table/ /Unspecified Salt/
…ACE inhibitors can enhance the efficacy of diuretics. This means that even very small doses of diuretics may significantly enhance the antihypertensive effect of ACE inhibitors; on the other hand, high doses of diuretics co-administered with angiotensin-converting enzyme inhibitors may lead to excessive blood pressure reduction and sodium loss in some patients. (ACE Inhibitor) (Salt Concentration Not Specified)
Oligopeptide drugs such as β-lactam antibiotics and angiotensin-converting enzyme inhibitors use the same carriers in humans and animals, which may lead to pharmacokinetic interactions. To simulate such interactions, this study investigated the effect of quinapril on the pharmacokinetics of cephalexin in rats. Serum cephalexin concentrations were determined by liquid chromatography, and data were analyzed using a non-compartmental model and a nonlinear mixed-effects model fitted to a two-compartmental model. A total of 5 groups, with 8 rats in each group, were tested. In the first three groups, the elimination kinetics of cephalexin after intra-arterial administration alone or in combination with parenteral or oral quinapril were studied, and no pharmacokinetic interactions were found. After parenteral administration, quinapril had no effect on the elimination of cephalexin, possibly because cephalexin has a higher affinity for the renal anion transport system than quinapril, or perhaps because the serum concentration of cephalexin is much higher than that of quinapril. In the latter two groups, oral administration was performed alone or in combination with quinapril, respectively. Following co-administration with quinapril, the mean area under the concentration-time curve (AUC) of cefalexin increased by approximately 30% (40.1 vs 31.4 mg·hr/L; P=0.04). Quinapril significantly reduced the mean elimination clearance of cefalexin from 0.81 L/h/kg body weight to 0.64 L/h/kg body weight (P<0.05), likely due to competitive inhibition of cefalexin secretion at the renal tubular level by quinapril. Quinapril significantly reduced the mean absorption rate constant of cefalexin (from 0.249 h⁻¹ to 0.177 h⁻¹; P<0.01), but did not alter the extent of absorption (89%). This pharmacokinetic interaction is likely due to competitive inhibition of active transport of cefalexin by quinapril at the intestinal level. /Unspecified salt/
Concomitant use of other antihypertensive drugs/ may produce an additive antihypertensive effect. /ACE Inhibitors/ /Unspecified Salts/
For more interaction (complete) data on quinapril hydrochloride (16 in total), please visit the HSDB record page.

---

Non-human Toxicity Values
LD50 (mg/kg) in male and female mice and rats: oral 1739, 1840, 4280, 3541; 504, 523, 158, 107 iv /Unspecified Salts/

---

Plasma Protein Binding: The plasma protein binding of quinapril hydrochloride (CI-906) is approximately 97%, and that of its active metabolite quinaprilat is approximately 95% [2]
-Adverse Reactions: The most common adverse reactions of quinapril hydrochloride (CI-906) in clinical studies included hypotension (especially in patients taking diuretics concurrently), dry cough, headache, dizziness, and fatigue. Rare adverse reactions include angioedema, hyperkalemia, and renal impairment (more common in patients with a history of renal impairment or heart failure) [1][2]
- Drug interactions:Quinapril hydrochloride (CI-906) Concomitant use with diuretics (e.g., furosemide) increases the risk of hypotension. Concomitant use with nonsteroidal anti-inflammatory drugs (NSAIDs, e.g., indomethacin) reduces the hypotensive effect ofquinapril hydrochloride (CI-906) and may increase the risk of renal impairment. Concomitant use with potassium-sparing diuretics (e.g., spironolactone) or potassium supplements increases the risk of hyperkalemia [1][2]

[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 the hydrochloride form produced by the reaction of equimolar amounts of quinapril with hydrogen chloride. It is a prodrug of quinapril hydrochloride (hydrolyzed by ethyl ester to the corresponding carboxylic acid) and is used as an angiotensin-converting enzyme inhibitor (ACE inhibitor) for the treatment of hypertension and congestive heart failure. It has antihypertensive activity and is also an EC 3.4.15.1 (peptidyl dipeptidase A) inhibitor. It contains a quinapril (1+) molecule. Quinapril hydrochloride is the hydrochloride form of quinapril, a prodrug and non-thiol angiotensin-converting enzyme (ACE) inhibitor with antihypertensive activity. Quinapril is hydrolyzed to its active form, quinapril, which binds to and inhibits ACE, thereby blocking the conversion of angiotensin I to angiotensin II. This eliminates the potent vasoconstrictive effect of angiotensin II, leading to vasodilation. Quinapril also reduces adrenal cortex aldosterone secretion for angiotensin II, thereby promoting diuresis and sodium excretion and increasing bradykinin levels.
A tetrahydroisoquinoline derivative and angiotensin-converting enzyme inhibitor used to treat hypertension and heart failure.
See also: quinapril (contains the active ingredient); quinaprilat (contains the active ingredient); hydrochlorothiazide; quinapril hydrochloride (one of the ingredients).

---

Mechanism of Action
Blocks the production of angiotensin II, promotes vasodilation and reduces aldosterone levels; simultaneously increases the levels of bradykinin and vasodilatory prostaglandins. /ACE inhibitor; (excerpt from table/ /unspecified salt content/)
Quinapril is deesterified to its major metabolite, quinaprilat, which is an inhibitor of angiotensin-converting enzyme (ACE) activity in humans and animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor angiotensin II. The mechanism of action of quinapril in treating hypertension and congestive heart failure (CHF) appears to primarily involve inhibiting ACE activity in circulation and tissues, thereby reducing the production of angiotensin II. Quinapril inhibits the increase in blood pressure induced by intravenous angiotensin I, but has no effect on the pressor response induced by angiotensin II, norepinephrine, or epinephrine. Angiotensin II also stimulates the adrenal cortex to secrete aldosterone, thereby promoting the reabsorption of sodium and fluid by the kidneys. Quinapril may cause a slight increase in serum potassium by reducing aldosterone secretion. In controlled hypertension trials, treatment with ACCUPRIL alone resulted in an average increase in serum potassium of 0.07 mmol/L… Eliminating the negative feedback effect of angiotensin II on renin secretion can lead to an increase in plasma renin activity (PRA). /Unspecified salt/

---

Therapeutic Use
…Quinapril has been shown to be very effective in treating hypertension… /Unspecified salt/
Angiotensin-converting enzyme (ACE) inhibitors appear to have a particular advantage in treating diabetic patients, slowing the progression of diabetic glomerulonephropathy. They have also been shown to be effective in slowing the progression of other types of chronic kidney disease, such as glomerulosclerosis, many of whom also have hypertension. For hypertensive patients with left ventricular hypertrophy, ACE inhibitors may be the first-line initial treatment. Patients with hypertension and ischemic heart disease are also suitable for ACE inhibitor therapy; this includes immediate use of ACE inhibitors after myocardial infarction, and studies have shown that this treatment can improve ventricular function and reduce morbidity and mortality. /ACE Inhibitors/ /Unspecified Salt/
Combination formulations of quinapril and hydrochlorothiazide are indicated for the treatment of hypertension. Fixed-dose combination formulations are generally not recommended for initial treatment, but can be used for maintenance therapy after the required dose has been determined to improve convenience, cost-effectiveness, and patient adherence. /Included in US Product Label/ /Unspecified Salt/
Angiotensin-Converting Enzyme (ACE) Inhibitors/ /Unspecified Salt/
For more complete data on the therapeutic uses of quinapril hydrochloride (6 types), please visit the HSDB record page.

---

Drug Warnings
Patients with serum creatinine ≥ 221 μmol/L (2.5 mg/dL) should have their dose reduced. /ACE Inhibitor; From Table/ /Unspecified Salt/
Hyperkalemia may occur in patients with renal insufficiency or those taking potassium-sparing diuretics. /ACE Inhibitor; From Table/ /Unspecified Salt/
Acute renal failure may occur in patients with severe bilateral renal artery stenosis or severe stenosis of a solitary renal artery. /ACE Inhibitor; From Table/ /Unspecified Salt/
In patients with impaired hepatic function, the conversion rate of quinapril to quinaprilat is reduced. /Unspecified Salt/
For more complete data on drug warnings for quinapril hydrochloride (of 12), please visit the HSDB record page.

---

Quinapril hydrochloride (CI-906) is an oral prodrug angiotensin-converting enzyme inhibitor (ACEI). Quinapril exerts its pharmacological effects by being metabolized into quinaprilat, which inhibits angiotensin-converting enzyme (ACE), thereby reducing the conversion of angiotensin I to angiotensin II (a potent vasoconstrictor) and increasing the level of bradykinin (a vasodilator) [1][2].
- Therapeutic indications: Quinapril hydrochloride (CI-906) is indicated for the treatment of essential hypertension (as a monotherapy or in combination with other antihypertensive drugs) and congestive heart failure (as a combination with diuretics and/or digoxin) [2].
- In hypertensive patients, oral administration of quinapril hydrochloride (CI-906) (10-40 mg once daily) results in a sustained reduction in systolic and diastolic blood pressure, with the peak antihypertensive effect occurring 2-4 hours after administration and lasting for more than 24 hours. [1][2]

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.)