Absorption, Distribution and Excretion
The bioavailability of quinapril is 50-80%. The time to peak concentration (Tmax) of quinapril is less than 1 hour, while that of quinapril is 2.5 hours. The peak plasma concentration (Cmax) of quinapril varies considerably among individuals, but in healthy men, a 10 mg dose can achieve a peak plasma concentration of 1526 ng/mL with an area under the curve (AUC) of 2443 ng·h/mL. A high-fat diet can reduce quinapril absorption by 25-30%. Up to 96% of quinapril is excreted in the urine. The excreted metabolites PD109488 and PD113413 each account for approximately 6% of the quinapril dose. A small portion of the dose recovered in the urine is unmetabolized quinapril. The mean volume of distribution of quinapril is 13.9 L. The clearance rate of quinapril is 68 mL/min.

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Metabolism / Metabolites
Quinapril undergoes deesterification to produce the active metabolite quinaprilat, or dehydration to produce the inactive metabolite PD109488. PD109488 can undergo O-deethylation to produce another inactive metabolite, PD113413. It is primarily metabolized by the liver. Elimination pathway: Quinaprilat is mainly excreted by the kidneys; 96% of the intravenously administered dose is excreted by the kidneys. Half-life: The elimination half-life is 2 hours, with the terminal phase extending to 25 hours.

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Biological Half-Life
The elimination half-life of the active metabolite quinaprilat is 2.3 hours.

Toxicity Summary
Overdose of ACE inhibitors can lead to severe hypotension, kidney failure, hyperkalemia, and hyponatremia. Severe hypotension can occur within the first 6 hours after taking 20 times the daily dose. If the patient presents within 1 hour of taking the medication, clinicians may consider using activated charcoal. Currently, there is no specific antidote for quinapril overdose. According to the manufacturer, hemodialysis and peritoneal dialysis may only significantly remove quinapril and its metabolites. Angiotensin II is a possible antidote for quinapril overdose. However, angiotensin II is currently only available in research facilities. Because quinapril causes hypotension through vasodilation and effective hypovolemia, infusion of normal saline may be helpful in treating quinapril overdose. For refractory hypotension, central venous catheter placement and norepinephrine administration may be necessary. ACE has two isoforms: the somatic isoform, a single-chain glycoprotein composed of 1277 amino acid residues; and the testicular isoform, with a lower molecular weight, believed to play a role in sperm maturation and sperm binding to fallopian tube epithelial cells. Somatic ACE possesses two functionally active domains, the N-domain and the C-domain, which are generated by tandem gene repetitions. Although these two domains have highly similar sequences, they perform different physiological functions. The C-domain is primarily involved in blood pressure regulation, while the N-domain is involved in the differentiation and proliferation of hematopoietic stem cells. ACE inhibitors can bind to and inhibit the activity of both domains, but have a higher affinity and inhibitory activity for the C-domain. Quinapril's main active metabolite, quinaprilat, competitively binds to ACE with angiotensin-converting enzyme I (ATI) and inhibits the enzymatic hydrolysis of ATI to angiotensin-converting enzyme II (ATIII). As described in the "Pharmacology" section above, lowering angiotensin II (ATII) levels in the body can lower blood pressure by inhibiting the pressor effect of ATII. Quinapril also leads to increased plasma renin activity, which may be due to loss of ATII-mediated feedback inhibition of renin release and/or through baroreceptor stimulation reflex mechanisms.

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Hepatotoxicity
Quinapril, like other ACE inhibitors, is associated with a low incidence of elevated serum transaminases (probability score: E* (unproven but suspected rare cause of clinically significant liver injury)).

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

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Protein Binding
Quinapril and its active metabolite quinaprilat have a protein binding rate of 97% in plasma.

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Toxicity Data
LD50 = 1739 mg/kg (oral administration to mice)

[1]. Quinapril--a preclinical review of the pharmacology, pharmacokinetics, and toxicology. Angiology. 1989 Apr;40(4 Pt 2):335-50.

Quinapril belongs to the isoquinoline class of compounds, with the chemical name (3S)-2-L-alanyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid, wherein the α-amino group of the alanyl residue is replaced by a 1-ethoxycarbonyl-4-phenylbut-2-yl group (all-S isomer). It is a prodrug of quinapril (obtained by ethyl ester hydrolysis to the corresponding carboxylic acid), used as an angiotensin-converting enzyme inhibitor (ACE inhibitor), typically in hydrochloride form for the treatment of hypertension and congestive heart failure. It has multiple functions, including as an EC 3.4.15.1 (peptidyl dipeptidase A) inhibitor, an antihypertensive drug, and a prodrug. It is a tertiary amide, ethyl ester, isoquinoline compound, and dicarboxylic acid monoester. Quinapril is the ethyl ester prodrug of the non-thiol angiotensin-converting enzyme inhibitor quinapril. It is used to treat hypertension and heart failure. Angiotensin-converting enzyme inhibitors are often used in combination with thiazide diuretics or beta-blockers as first-line treatments for hypertension. Quinapril was approved by the U.S. Food and Drug Administration (FDA) on November 19, 1991. Its combination tablets with hydrochlorothiazide were also approved on December 28, 1999. Quinapril is an angiotensin-converting enzyme inhibitor. Its mechanism of action is as an angiotensin-converting enzyme inhibitor. Quinapril is an angiotensin-converting enzyme (ACE) inhibitor used to treat hypertension and congestive heart failure. Quinapril is associated with a low incidence of transient elevations in serum transaminases, but no association has been found with cases of acute liver injury. Quinapril is a prodrug, belonging to the non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitors, and has an antihypertensive effect. Quinapril is hydrolyzed to its active form, quinaprilat, which binds to ACE and inhibits its activity, 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 in response to angiotensin II, thereby promoting diuresis and sodium excretion, and increasing bradykinin levels. Quinapril is a prodrug belonging to the angiotensin-converting enzyme (ACE) inhibitor class. After oral administration, it is metabolized to quinapril (quinapril dicarboxylate). Quinapril is a competitive inhibitor of angiotensin-converting enzyme (ACE), an enzyme responsible for converting angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Quinapril can be used to treat essential hypertension and congestive heart failure.
A tetrahydroisoquinoline derivative and angiotensin-converting enzyme inhibitor used to treat hypertension and heart failure.
See also: Lisinopril (related drugs); Enalapril (related drugs); Quinapril hydrochloride (salt form)...See more...

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Drug Indication
Quinapril is used to treat hypertension and can also be used as an adjunct therapy for heart failure. Quinapril is used in combination with hydrochlorothiazide to treat hypertension. Quinapril is an angiotensin-converting enzyme (ACE) inhibitor developed in the 1980s. Researchers have found that quinapril has a lower incidence of adverse reactions compared to other ACE inhibitors (such as captopril and enalapril) and the thiazide diuretic chlorthalidone. Quinapril can effectively lower systolic blood pressure by 13 mmHg and diastolic blood pressure by 10 mmHg in approximately two-thirds of patients.

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Mechanism of Action
Angiotensin II constricts coronary arteries and has a positive inotropic effect, which under normal circumstances increases vascular resistance and oxygen consumption. This effect can ultimately lead to cardiomyocyte hypertrophy and vascular smooth muscle cell proliferation. Angiotensin II also stimulates the production of plasminogen activator inhibitor-1 (PAI-1), thereby increasing the risk of thrombosis. Quinapril prevents the conversion of angiotensin I to angiotensin II by inhibiting angiotensin-converting enzyme and reduces the breakdown of bradykinin. Lower angiotensin II levels lead to lower PAI-1 levels, thereby reducing the risk of thrombosis, especially after myocardial infarction.

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Pharmacodynamics
Quinapril is a prodrug of angiotensin-converting enzyme (ACE) inhibitors, used to treat hypertension or as an adjunct therapy for heart failure. Quinapril has a wide therapeutic window and a long duration of action, and is administered once daily at a dose of 10-80 mg.

C25H30N2O5

438.52

438.215

85441-61-8

Quinapril hydrochloride;82586-55-8;Quinapril-d5;1279029-79-6

54892

Typically exists as solids at room temperature

1.217 g/cm3

662ºC

120-130 °C ; 120 - 130 °C

354.1ºC

2.896

2

6

10

32

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

JSDRRTOADPPCHY-HSQYWUDLSA-N

InChI=1S/C25H30N2O5/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)/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

CI-906 free acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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