Ramipril

Pharmaceuticals -> Antihypertensives

Pharmaceuticals -> Listed in ZINC15

2.9

1.05

Felty needles from ether

White crystalline solid

3.5mg/L

Sparingly soluble in water

Freely soluble in methanol

Soluble in polar substances and buffered aqueous solutions

3.90e-02 g/L

>62.5 [ug/mL] (The mean of the results at pH 7.4)

Breast Feeding; Lactation; Milk, Human; Antihypertensive Agents; Angiotensin-Converting Enzyme Inhibitors; ACE Inhibitors; ACEIs

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

109 °C

MP: 105-112 °C

109 °C

197 Ų [M+H]+ [CCS Type: TW; Method: Major Mix IMS/Tof Calibration Kit (Waters)]

190.24 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

This chemical does not meet GHS hazard criteria for 1.3% (1 of 76) of reports.

Danger

H360 (93.4%): May damage fertility or the unborn child [Danger Reproductive toxicity]

P203, P280, P318, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 76 reports by companies from 13 notifications to the ECHA C&L Inventory.

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

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.

Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary.

Store at 20 deg to 25 °C (68 deg to 77 °F).

Keep container tightly closed in a dry and well-ventilated place.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Avoid breathing vapors, mist or gas. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal.

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company; Contaminated packaging: Dispose of as unused product.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Avoid dust formation. Avoid breathing vapors, mist or gas. Environmental precautions: Do not let product enter drains.

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

Precautions for safe handling: Provide appropriate exhaust ventilation at places where dust is formed.

Appropriate engineering controls: General industrial hygiene practice.

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.

Eye/face protection: Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).

Skin protection: Handle with gloves.

Body Protection: Choose body protection in relation to its type, to the concentration and amount of dangerous substances, and to the specific work-place.

Respiratory protection: Respiratory protection is not required. Where protection from nuisance levels of dusts are desired, use type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of non-ateroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 (COX-2) inhibitors, with angiotensin-converting enzyme (ACE) inhibitors, including ramipril, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving ramipril and NSAID therapy. The antihypertensive effect of ACE inhibitors, including ramipril, may be attenuated by NSAIDs.

Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving ACE inhibitors during therapy with lithium; therefore, frequent monitoring of serum lithium levels is recommended. If a diuretic is also used, the risk of lithium toxicity may be increased.

Coadministration of ramipril with other drugs that raise serum potassium levels may result in hyperkalemia. Monitor serum potassium in such patients.

Patients on diuretics, especially those in whom diuretic therapy was recently instituted, may occasionally experience an excessive reduction of blood pressure after initiation of therapy with ramipril. The possibility of hypotensive effects with ramipril can be minimized by either decreasing or discontinuing the diuretic or increasing the salt intake prior to initiation of treatment with ramipril. If this is not possible, reduce the starting dose.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 2000(SRC), determined from a structure estimation method(2), indicates that ramipril is expected to have low mobility in soil(SRC). The estimated pKa values of ramipril are 3.74 and 5.15(3), indicating that this compound will exist almost entirely exist in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the compound exists as an anion and anions do not volatilize. Ramipril is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.8X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2017).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 2000(SRC), determined from a structure estimation method(2), indicates that ramipril is expected to adsorb to suspended solids and sediment(SRC). Estimated pKa values of 3.74 and 5.15(3) indicate ramipril will exist almost entirely in the anion form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(4), an estimated BCF of 3(SRC), from an estimated log Kow of 3.32(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2017).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), ramipril, which has an estimated vapor pressure of 3.8X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase ramipril may be removed from the air by wet and dry deposition(SRC). Ramipril contains chromophores that absorb at wavelengths >290 nm(4) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

IDENTIFICATION AND USE: Ramipril is a prodrug and has little pharmacologic activity until hydrolyzed in the liver to ramiprilat. It is an angiotensin-converting enzyme (ACE) inhibitor indicated for the treatment of hypertension. It is also used for stable patients with demonstratable congestive heart failure within the first few days of sustaining acute myocardial infarction. HUMAN STUDIES: Rare ACE inhibitor-associated clinical syndrome manifested initially by cholestatic jaundice may occur. It may progress to fulminant hepatic necrosis and is potentially fatal. Patients receiving an ACE inhibitor, including ramipril, who develop jaundice or marked elevations in hepatic enzymes should discontinue the drug and receive appropriate monitoring. Sensitivity reactions, including anaphylactic reactions and angioedema (including laryngeal or tongue edema) are potentially fatal. Head and neck angioedema involving the tongue, glottis, or larynx may cause airway obstruction. If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, ramipril should be discontinued and appropriate therapy (e.g., epinephrine) should be initiated immediately. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue ramipril as soon as possible. No mutagenic activity was detected in the unscheduled DNA synthesis in a human cell line. ANIMAL STUDIES: No evidence of a tumorigenic effect was found when ramipril was given by gavage to rats for up to 24 months at doses of up to 500 mg/kg/day or to mice for up to 18 months at doses of up to 1000 mg/kg/day. A study in rats with dosages as great as 500 mg/kg/day did not produce adverse effects on fertility. Kidney organogenesis and functional development continue well into the postnatal period in the rat. A within-litter design was used to characterize renal susceptibility to an ACE inhibitor during the third week of life in rats. There were no treatment-related effects in rats dosed on PND 21. Following dosing on PND 14, dose-related increases were noted in mean serum urea nitrogen and/or creatinine levels on PND 17, but these measures recovered by PND 28. The interim changes were accompanied by macroscopic and microscopic changes in the kidneys on PND 17, including tubular hypoplasia, renal papillary edema, cortical tubular dilatation, hydronephrosis (pelvic dilatation) and tubular basophilia; renal anatomic changes were still evident and more severe on PND 28, 14 days after dosing. No mutagenic activity was detected in the Ames test in bacteria, the micronucleus test in mice or a forward gene-mutation assay in a Chinese hamster ovary cell line.

Ramipril overdose can lead to severe hypotension, primarily attributed to vasodilation and effective hypovolemia. A study conducted in 2006 to investigate the effects of ramipril overdose on blood pressure concluded that a drop in blood pressure typically occurs within the first 4 to 4.5 hours after ingestion. Therefore, monitoring the patient for at least 6 hours after the overdose is essential. If the blood pressure remains stable during the first 6 hours after administration, the patient can be considered for discharge.

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of November 16, 2017: http://actor.epa.gov/dashboard/]

Using a structure estimation method based on molecular connectivity indices(1), the Koc of ramipril can be estimated to be 2000(SRC). According to a classification scheme(2), this estimated Koc value suggests that ramipril is expected to have low mobility in soil. The estimated pKa values of ramipril 3.74 and 5.15(3), indicating that this compound will exist almost entirely in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

/SIGNS AND SYMPTOMS/ Rare angiotensin-converting enzyme (ACE) inhibitor-associated clinical syndrome manifested initially by cholestatic jaundice may occur; may progress to fulminant hepatic necrosis and is potentially fatal. Patients receiving an ACE inhibitor, including ramipril, who develop jaundice or marked elevations in hepatic enzymes should discontinue the drug and receive appropriate monitoring.

/SIGNS AND SYMPTOMS/ Like other angiotensin-converting enzyme (ACE) inhibitors, ramipril rarely is associated with hypotension in patients with uncomplicated hypertension. Symptomatic hypotension may occur; patients at particular risk include those with severe volume and/or salt depletion secondary to prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea, or vomiting. Volume and/or salt depletion should be corrected before starting ramipril therapy. Marked hypotension may occur in patients with heart failure (with or without associated renal impairment), which may be associated with oliguria and/or progressive azotemia and, rarely, acute renal failure and/or death. In patients with heart failure, ramipril therapy should be started under close medical supervision, and patients should be followed closely for at least 2 weeks after initiation of ramipril or diuretic therapy or dosage adjustment of either drug.

/SIGNS AND SYMPTOMS/ Sensitivity reactions, including anaphylactic reactions and angioedema (including laryngeal or tongue edema) are potentially fatal. Head and neck angioedema involving the tongue, glottis, or larynx may cause airway obstruction. If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, ramipril should be discontinued and appropriate therapy (e.g., epinephrine) should be initiated immediately.

/CASE REPORTS/ ... /The purpose of this study was/ to describe 3 patients who developed hepatitis, with or without jaundice, after receiving ramipril. Medical records and liver biopsies of the 3 patients were reviewed. Clinical, laboratory, and histologic findings were compared with findings in other cases of angiotensin-converting enzyme inhibitor-induced liver injury reported in the literature. The 3 patients were middle-aged men. In 2 patients, jaundice appeared 4 and 8 weeks after starting ramipril. Bilirubin levels peaked at 15.5 and 5 mg/dL, and alkaline phosphatase values peaked at 957 and 507 U/L. Aminotransferase levels were mildly elevated. Endoscopic retrograde cholangiopancreatography and ultrasonography showed no bile duct obstruction. Liver biopsies from the jaundiced patients were similar, with cholestasis, duct necrosis, and extravasation of bile, ductular proliferation, and portal inflammation. Cholestasis improved in 1 patient 6 weeks after stopping ramipril and was prolonged for 14 months in the other, in whom biliary cirrhosis was present on biopsy. The third patient developed hepatitis without jaundice 3 weeks after starting ramipril; symptoms resolved after stopping the drug. Ramipril-associated liver injury is similar to that seen with other angiotensin-converting enzyme inhibitors, but liver biopsy findings of duct necrosis and extravasation of bile have not been reported previously. Prolonged cholestatic hepatitis and biliary cirrhosis may result from the use of ramipril. Monitoring of liver enzymes is advisable for patients starting on ramipril.

For more Human Toxicity Excerpts (Complete) data for Ramipril (9 total), please visit the HSDB record page.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Ramipril

vLess-DILI-concern

7

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

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

C09AA05

C - Cardiovascular system

QC - Cardiovascular system

Ramipril is an ACE inhibitor similar to benazepril, fosinopril and quinapril. It is an inactive prodrug that is converted to ramiprilat in the liver, the main site of activation, and kidneys. Ramiprilat confers blood pressure lowing effects by antagonizing the effect of the RAAS. The RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from the granular cells of the juxtaglomerular apparatus in the kidneys. In the blood stream, renin cleaves circulating angiotensinogen to ATI, which is subsequently cleaved to ATII by ACE. ATII increases blood pressure using a number of mechanisms. First, it stimulates the secretion of aldosterone from the adrenal cortex. Aldosterone travels to the distal convoluted tubule (DCT) and collecting tubule of nephrons where it increases sodium and water reabsorption by increasing the number of sodium channels and sodium-potassium ATPases on cell membranes. Second, ATII stimulates the secretion of vasopressin (also known as antidiuretic hormone or ADH) from the posterior pituitary gland. ADH stimulates further water reabsorption from the kidneys via insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. Third, ATII increases blood pressure through direct arterial vasoconstriction. Stimulation of the Type 1 ATII receptor on vascular smooth muscle cells leads to a cascade of events resulting in myocyte contraction and vasoconstriction. In addition to these major effects, ATII induces the thirst response via stimulation of hypothalamic neurons. ACE inhibitors inhibit the rapid conversion of ATI to ATII and antagonize RAAS-induced increases in blood pressure. ACE (also known as kininase II) is also involved in the enzymatic deactivation of bradykinin, a vasodilator. Inhibiting the deactivation of bradykinin increases bradykinin levels and may sustain the effects of ramiprilat by causing increased vasodilation and decreased blood pressure.

Ramipril inhibits the RAAS system by binding to and inhibiting ACE thereby preventing the conversion of angiotensin I to angiotensin II. As plasma levels of angiotensin II fall, less activation of the G-protein coupled receptors angiotensin receptor I (AT₁R) and angiotensin receptor II (AT₂R) occurs. AT₁R mediates vasoconstriction, inflammation, fibrosis, and oxidative stress through a variety of signaling pathways. These include G_q coupling to the inositol triphosphate pathway, activation of phospholipases C, A₂, and D which contribute to eicosanoid production, activation of Ca²⁺-dependent and MAP kinases, G_i and G_12/13, and eventual activation of the Jak/STAT pathway leading to cell growth and production of extracellular matrix components. AT₁R activation also leads to increased activity of membrane-bound NADH/NADPH oxidase which contributes to production of reactive oxygen species. Decreased activation of this receptor mediates the renoprotective, antihypertensive, and cardioprotective effects of ramipril by reducing inflammation and vasoconstriction. AT₂R acts in opposition to the effects of AT₁R by activating phosphotyrosine phosphatases which inhibit MAP kinases, inhibiting Ca²⁺ channel opening, and stimulating cGMP and nitric oxide production leading to vasodilation. These counteracting effects are shared by the Mas receptor which is activated by Ang(1-7), a subtype of angiotensin produced by plasma esterases from AngI or by ACE2 from AngII produced through a secondary pathway by tonin and cathepsin G. Ang(1-7) also activates AT₂R although the bulk of its effect is mediated by MasR. ACE is also responsible for the breakdown of bradykinin. The resulting buildup of bradykinin due to ACE inhibition is thought to mediate the characteristic dry-cough as a side effect of ACE inhibitor medications.

Plasma concentrations of ramiprilat decline in a triphasic manner. Initial rapid decline represents distribution into tissues and has a half life of 2-4 hours. The half life of the apparent elimination phase is 9-18 hours, which is thought to represent clearance of free drug. The half-life of the terminal elimination phase is > 50 hours and thought to represent clearance of drug bound to ACE due to its slow dissociation. The half life of ramiprilat after multiple daily doses (MDDs) is dose-dependent, ranging from 13-17 hours with 5-10 mg MDDs to 27-36 hours for 2.5 mg MDDs.

Plasma concentrations of ramiprilat /metabolite of ramipril/ decline in a triphasic manner (initial rapid decline, apparent elimination phase, terminal elimination phase). The initial rapid decline, which represents distribution of the drug into a large peripheral compartment and subsequent binding to both plasma and tissue ACE, has a half-life of 2 to 4 hours. Because of its potent binding to ACE and slow dissociation from the enzyme, ramiprilat shows two elimination phases. The apparent elimination phase corresponds to the clearance of free ramiprilat and has a half-life of 9 to 18 hours. The terminal elimination phase has a prolonged half-life (>50 hours) and probably represents the binding/dissociation kinetics of the ramiprilat/ACE complex. It does not contribute to the accumulation of the drug. After multiple daily doses of ramipril 5 mg to 10 mg, the half-life of ramiprilat concentrations within the therapeutic range was 13 to 17 hours. /Ramiprilat/

Hepatic metabolism accounts for 75% of total ramipril metabolism. 25% of hepatic metabolism produces the active metabolite ramiprilat via liver esterase enzymes. 100% of renal metabolism converts ramipril to ramiprilat. Other metabolites, diketopiperazine ester, the diketopiperazine acid, and the glucuronides of ramipril and ramiprilat, are inactive.

Cleavage of the ester group (primarily in the liver) converts ramipril to its active diacid metabolite, ramiprilat. Peak plasma concentrations of ramiprilat are reached 2 to 4 hours after drug intake. The serum protein binding of ramipril is about 73% and that of ramiprilat about 56%; in vitro, these percentages are independent of concentration over the range of 0.01 ug/mL to 10 mcg/mL.

After oral administration to dogs, ramipril is rapidly converted via de-esterification into ramiprilat. Bioavailability of ramiprilat after a dose of 0.25 mg/kg per day of ramipril is approximately 6.7%.

Ramipril is a prodrug and has little pharmacologic activity until hydrolyzed in the liver to ramiprilat.

Ramipril is almost completely metabolized to ramiprilat, which has about 6 times the angiotensin-converting enzyme (ACE) inhibitory activity of ramipril, and to the diketopiperazine ester, the diketopiperazine acid, and the glucuronides of ramipril and ramiprilat, all of which are inactive.

L35JN3I7SJ

RAMIPRIL

Established Pharmacologic Class [EPC] - Angiotensin Converting Enzyme Inhibitor

Mechanisms of Action [MoA] - Angiotensin-converting Enzyme Inhibitors

Ramipril is an Angiotensin Converting Enzyme Inhibitor. The mechanism of action of ramipril is as an Angiotensin-converting Enzyme Inhibitor.

RAMIPRIL

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.

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.

The extent of absorption is at least 50-60%.. Food decreases the rate of absorption from the GI tract without affecting the extent of absorption. The absolute bioavailabilities of ramipril and ramiprilat were 28% and 44%, respectively, when oral administration was compared to intravenous administration. The serum concentration of ramiprilat was unchanged when capsules were opened and the contents dissolved in water, dissolved in apple juice, or suspended in apple sauce.

Following oral administration, about 60% of the dose is eliminated in the urine as unchanged ramipril (<2%) and its metabolites. About 40% of the dose is found in the feces, representing both unabsorbed drug and drugs and metabolites eliminated via biliary excretion. The urinary excretion of ramipril may be reduced in patients with impaired renal function.

The renal clearance of ramipril and ramiprilat was reported to be 7.2 and 77.4 mL/min/1.73m². The mean renal clearance of ramipril and ramiprilat is reported to be 10.7 and 126.8 mL/min in healthy elderly patients with normal renal function, additionally the Cmax of ramiprilat is approximately 20% higher in this population. While the pharmacokinetics of ramipril appear unaffected by reduced renal function, the plasma concentration and half-life of ramiprilat are increased. In patient's with hepatic failure the concentration of ramipril is initially increased while the tmax of ramiprilat is prolonged due to a reduced ability to metabolize the drug. However, steady state concentrations of ramiprilat are the same in hepatic failure as in healthy patients.

/MILK/ Ingestion of a single 10 mg oral dose of ramipril resulted in undetectable amounts of ramipril and its metabolites in breast milk.

Following oral administration of ramipril, peak plasma concentrations (Cmax) of ramipril are reached within 1 hour. The extent of absorption is at least 50% to 60%, and is not significantly influenced by the presence of food in the gastrointestinal tract, although the rate of absorption is reduced.

Plasma concentrations of ramiprilat decline in a triphasic manner (initial rapid decline, apparent elimination phase, terminal elimination phase). The initial rapid decline, which represents distribution of the drug into a large peripheral compartment and subsequent binding to both plasma and tissue ACE, has a half-life of 2 to 4 hours. Because of its potent binding to ACE and slow dissociation from the enzyme, ramiprilat shows two elimination phases. The apparent elimination phase corresponds to the clearance of free ramiprilat and has a half-life of 9 to 18 hours. The terminal elimination phase has a prolonged half-life (>50 hours) and probably represents the binding/dissociation kinetics of the ramiprilat/ACE complex. It does not contribute to the accumulation of the drug. After multiple daily doses of ramipril 5 mg to 10 mg, the half-life of ramiprilat concentrations within the therapeutic range was 13 to 17 hours. /Ramiprilat/

MEDICATION

MEDICATION (VET)

Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents

Use (kg; approx.) in Germany (2009): >10000