Eprosartan

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Antihypertensives

Pharmaceuticals -> Used in Switzerland

Pharmaceuticals

Insoluble (mesylate form)

8.66e-03 g/L

248-250 °C (mesylate form)

260-261 °C

248 - 250 °C (mesylate form)

White to off-white crystalline powder, mp 248-250 °C. Insoluble in water. Freely soluble in ethanol /Eprosartan monomethanesulfonate/

White or practically white, crystalline powder, MW 297.74. Slightly soluble in water, freely soluble in sodium hydroxide solution. /Mesylate-hydrochlorothiazide/

Warning

H315: Causes skin irritation [Warning Skin corrosion/irritation]

P264, P264+P265, P280, P302+P352, P305+P351+P338, P321, P332+P317, P337+P317, and P362+P364 (click each P-code to see the statement)

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

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 controlled room temperature 20 to 25 °C (68 to 77 °F).

Conditions for safe storage, including any incompatibilities: Keep container tightly closed in a dry and well-ventilated place.

Accidental Release Measures. Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapours, mist or gas. Ensure adequate ventilation. Avoid breathing dust. 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.

SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

Waste treatment methods. Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Contaminated packaging: Dispose of as unused product.

Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection.

Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.

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.

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.

Eye/face protection: Safety glasses with side-shields conforming to EN166 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: Impervious clothing, The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.

Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator. For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).

Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor agonists. Monitor serum lithium levels during concomitant use.

Do not co-administer aliskiren with Teveten in patients with diabetes. Avoid use of aliskiren with Teveten in patients with renal impairment (GFR <60 mL/min).

Dual blockade of the renin-angiotensin system (RAS) with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on Teveten and other agents that affect the RAS.

Potential pharmacologic interaction (attenuated hypotensive effects) when angiotensin II receptor antagonists are used concomitantly with nonsteroidal anti-inflammatory agents (NSAIAs), including selective cyclooxygenase-2 (COX-2) inhibitors. Possible deterioration of renal function in geriatric, volume-depleted (including those receiving concomitant diuretic therapy), or renally impaired patients; renal function should be monitored periodically in patients receiving concomitant therapy with eprosartan and an NSAIA, including selective COX-2 inhibitors.

For more Interactions (Complete) data for EPROSARTAN (7 total), please visit the HSDB record page.

IDENTIFICATION AND USE: Eprosartan is a white to off-white crystalline powder that is formulated into oral tablets. Eprosartan is an angiotensin II type 1 (AT1) receptor antagonist. It is used alone or in combination with other classes of antihypertensive agents in the management of hypertension. HUMAN EXPOSURE AND TOXICITY: The use of eprosartan during pregnancy is contraindicated. While use during the first trimester does not suggest a risk of major anomalies, use during the second and third trimester may cause teratogenicity and severe fetal and neonatal toxicity. Fetal toxic effects may include anuria, oligohydramnios, fetal hypocalvaria, intrauterine growth restriction, premature birth, and patent ductus arteriosus. Anuria-associated oligohydramnios may produce fetal limb contractures, craniofacial deformation, and pulmonary hypoplasia. Severe anuria and hypotension that are resistant to both pressor agents and volume expansion may occur in the newborn following in utero exposure to eprosartan. In human peripheral lymphocytes in vitro, eprosartan was equivocal for clastogenicity with metabolic activation, and was negative without metabolic activation. In the same assay, eprosartan was positive for polyploidy with metabolic activation and equivocal for polyploidy without metabolic activation. ANIMAL STUDIES: Eprosartan was not carcinogenic in dietary restricted rats or ad libitum fed mice dosed at 600 mg and 2000 mg/kg/day, respectively, for up to 2 years. Also, the reproductive performance of male and female rats was unaffected by administration of eprosartan. No adverse effects on in utero or postnatal development and maturation of offspring were observed when eprosartan was administered to pregnant rats at oral doses up to 1000 mg /kg/day. Eprosartan has been shown to produce maternal and fetal toxicities (maternal and fetal mortality, low maternal body weight and food consumption, resorptions, abortions and litter loss) in pregnant rabbits given oral doses. Eprosartan was not mutagenic in vitro in bacteria or mammalian cells (mouse lymphoma assay). Eprosartan also did not cause structural chromosomal damage in vivo (mouse micronucleus assay).

/SIGNS AND SYMPTOMS/ The most likely manifestations of overdosage are hypotension and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. Hyperkalemia may also occur in patients with renal disease or in patients taking potassium-sparing medications. /Angiotensin receptor blockers/

/GENOTOXICITY/ In human peripheral lymphocytes in vitro , eprosartan mesylate was equivocal for clastogenicity with metabolic activation, and was negative without metabolic activation. In the same assay, eprosartan mesylate was positive for polyploidy with metabolic activation and equivocal for polyploidy without metabolic activation.

/OTHER TOXICITY INFORMATION/ ... Nine healthy subjects were studied in high sodium balance (ie, sodium intake 200 mmol/d). On the first day, the subjects received 600 mg eprosartan orally, and renal plasma flow and glomerular filtration rate were measured. Glucose was infused intravenously on the second and third study days to increase plasma glucose to a level below the threshold for glycosuria (approximately 8.8 mmol/L). Eprosartan at a dose of 600 mg or placebo was administered randomly on the second or third study day 1 hour after initiation of glucose infusion. Renal plasma flow increased (by 76+/-7 mL. min(-1). 1.73 m(-2), P<0.01) in response to sustained moderate hyperglycemia and then increased further (by 147+/-15 mL. min(-1). 1.73 m(-2), P<0.01) when eprosartan was administered during hyperglycemia. Eprosartan, conversely, did not affect renal plasma flow and glomerular filtration rate in normoglycemic subjects. Glomerular filtration rate was not affected by either hyperglycemia or eprosartan. Neither plasma renin activity nor plasma Ang II concentration changed during hyperglycemia, suggesting that the hormonal responses responsible for the enhanced renal vasodilator response to eprosartan occurred within the kidney. The enhancement of the renal vasodilator effect of eprosartan during hyperglycemia is consistent with activation of the intrarenal renin-angiotensin system.

/OTHER TOXICITY INFORMATION/ In July 2010, the US Food and Drug Administration (FDA) initiated a safety review of angiotensin II receptor antagonists after a published meta-analysis suggested a possible association between the use of these agents and an increased risk of cancer. The meta-analysis, which combined cancer-related findings from 5 randomized, controlled trials in over 60,000 patients, found a modest but significant increase in the risk of new cancer occurrence in patients receiving an angiotensin II receptor antagonist (mostly telmisartan) compared with those in control groups (7.2 versus 6%, respectively; risk ratio 1.08). However, because of several limitations of the study (e.g., trials included in the meta-analysis were not specifically designed to evaluate cancer outcomes, lack of individual patient data), the validity of these findings has been questioned. Subsequent studies, including a larger, more comprehensive meta-analysis conducted by FDA, have not shown an increased risk of cancer in patients receiving angiotensin II receptor antagonists. FDA's meta-analysis, which included trial-level data from 31 randomized studies (total of approximately 156,000 patients), found no evidence of an increased risk of cancer in patients who received an angiotensin II receptor antagonist compared with those who received other treatments (placebo or active control). The overall rate of new cancer occurrence was essentially the same in both groups of patients (1.82 and 1.84 cases per 100 patient-years, respectively). In addition, there was no difference in the risk of cancer-related death, breast cancer, lung cancer, or prostate cancer between the groups. Based on these results and a review of all currently available data related to this potential safety concern, FDA has concluded that use of angiotensin II receptor antagonists is not associated with an increased risk of cancer.

For more Human Toxicity Excerpts (Complete) data for EPROSARTAN (6 total), please visit the HSDB record page.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

eprosartan

DILI Negative

Oral

DOI:10.1016/j.drudis.2019.09.022

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Eprosartan mesylate was not carcinogenic in dietary restricted rats or ad libitum fed mice dosed at 600 mg and 2000 mg eprosartan/kg/day, respectively, for up to 2 years.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ No adverse effects on in utero or postnatal development and maturation of offspring were observed when eprosartan mesylate was administered to pregnant rats at oral doses up to 1000 mg eprosartan/kg/day (the 1000 mg eprosartan/kg/day dose in non-pregnant rats yielded systemic exposure to unbound eprosartan approximately 0.6 times the exposure achieved in humans given 400 mg b.i.d.).

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Eprosartan mesylate has been shown to produce maternal and fetal toxicities (maternal and fetal mortality, low maternal body weight and food consumption, resorptions, abortions and litter loss) in pregnant rabbits given oral doses as low as 10 mg eprosartan/kg/day. No maternal or fetal adverse effects were observed at 3 mg/kg/day; this oral dose yielded a systemic exposure (AUC) to unbound eprosartan 0.8 times that achieved in humans given 400 mg b.i.d.

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Eprosartan mesylate had no adverse effects on the reproductive performance of male or female rats at oral doses up to 1000 mg eprosartan/kg/day. This dose provided systemic exposure (AUC) to unbound eprosartan approximately 0.6 times the exposure achieved in humans given 400 mg b.i.d.

/GENOTOXICITY/ Eprosartan mesylate was not mutagenic in vitro in bacteria or mammalian cells (mouse lymphoma assay). Eprosartan mesylate also did not cause structural chromosomal damage in vivo (mouse micronucleus assay).

Facial edema occurred in patients receiving eprosartan. Sensitivity reactions including various anaphylactoid reactions and/or angioedema have been reported in patients receiving other angiotensin II receptor antagonists. Eprosartan is not recommended in patients with a history of angioedema associated with or unrelated to ACE inhibitor or angiotensin II receptor antagonist therapy.

Do not co-administer aliskiren with Teveten in patients with diabetes. Avoid use of aliskiren with Teveten in patients with renal impairment (GFR <60 mL/min).

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.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

Treatment and supportive measures. Monitor blood pressure and heart rate for 6 hours after ingestion. If symptomatic or significant hypotension develops, observe for at least 24 hours. 1. If hypotension occurs, treat it with supine positioning and IV fluids. Vasopressors are rarely necessary. 2. Treat angioedema with usual measures (eg, diphenhydramine, corticosteroids) and discontinue the ACE inhibitors. Switching to an AR blocker may not be appropriate as angioedema has also been reported with these agents. 3. Treat hyperkalemia if it occurs. /Angiotensin blockers and ACE inhibitors/

For more Antidote and Emergency Treatment (Complete) data for EPROSARTAN (6 total), please visit the HSDB record page.

Eprosartan

9.3

39.4

Eprosartan mesylate can be administered once or twice daily with total daily doses ranging from 400 mg to 800 mg.

Data used to generate the benchmarks include the following: Lowest Daily Dose (LDD): 400 mg/day, Lowest Therapeutic Dose (LTD): 5.0 mg/kg-day, and Screening Dose: 0.0017 mg/kg-day.

3-Jan-12

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

C09CA02

C - Cardiovascular system

QC - Cardiovascular system

Angiotensin II, the principal pressor agent of the renin-angiotensin system, is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme [kininase II]. It is responsible for effects such as vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Eprosartan selectively blocks the binding of angiotensin II to the AT₁ receptor, which in turn leads to multiple effects including vasodilation, a reduction in the secretion of vasopressin, and reduction in the production and secretion of aldosterone. The resulting effect is a decrease in blood pressure.

Eprosartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT₁ receptor found in many tissues (e.g., vascular smooth muscle, adrenal gland). There is also an AT₂ receptor found in many tissues but it is not known to be associated with cardiovascular homeostasis. Eprosartan does not exhibit any partial agonist activity at the AT₁ receptor. Its affinity for the AT₁ receptor is 1,000 times greater than for the AT₂ receptor. In vitro binding studies indicate that eprosartan is a reversible, competitive inhibitor of the AT₁ receptor. Eprosartan has also been shown to bind to AT₁ receptors both presynaptically and synaptically. Its action on presynaptic AT₁ receptors results in the inhibition of sympathetically stimulated noradrenaline release. Unlike ACE inhibitors, eprosartan and other ARBs do not interfere with response to bradykinins and substance P, which allows for the absence of adverse effects that are present in ACE inhibitors (eg. dry cough).

Angiotensin II (AII) receptor blockers offer an alternative means of blocking the renin-angiotensin-aldosterone system (RAAS) to angiotensin converting enzyme (ACE) inhibitors. Being highly selective for the AII receptor subtype AT(1), AII receptor blockers may avoid side-effects associated with ACE inhibitor treatment, such as cough. Eprosartan is a non-biphenyl, non-tetrazole competitive blocker that is chemically distinct from other AII receptor blockers, which may account for differences in its pharmacological properties. It induces dual blockade of AT(1) receptors both presynaptically and postsynaptically, reducing sympathetic nerve activity to a significantly greater degree than other AT(1) receptor blockers. ...

Angiotensin II (formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (kininase II)), a potent vasoconstrictor, is the principal pressor agent of the renin-angiotensin system. Angiotensin II also stimulates aldosterone synthesis and secretion by the adrenal cortex, cardiac contraction, renal resorption of sodium, activity of the sympathetic nervous system, and smooth muscle cell growth. Eprosartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor found in many tissues (e.g., vascular smooth muscle, adrenal gland). There is also an AT2 receptor found in many tissues but it is not known to be associated with cardiovascular homeostasis. Eprosartan does not exhibit any partial agonist activity at the AT1 receptor. Its affinity for the AT1 receptor is 1,000 times greater than for the AT2 receptor. In vitro binding studies indicate that eprosartan is a reversible, competitive inhibitor of the AT1 receptor. Blockade of the AT1 receptor removes the negative feedback of angiotensin II on renin secretion, but the resulting increased plasma renin activity and circulating angiotensin II do not overcome the effect of eprosartan on blood pressure. Teveten does not inhibit kininase II, the enzyme that converts angiotensin I to angiotensin II and degrades bradykinin; whether this has clinical relevance is not known. It does not bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.

Selective blockade of the angiotensin II AT1 receptor represents a novel mechanism for interrupting the renin-angiotensin system without altering the potential benefits of AT2 receptor stimulation. This selective inhibition produces none of the disadvantages associated with reduced bradykinin metabolism and angiotensin II generated by non-angiotensin-converting enzyme pathways. Eprosartan is a potent (1.4 nmol/L) AT1 receptor antagonist that competitively blocks angiotensin II-induced vascular contraction. In various animal models of disease, including hypertension and stroke, eprosartan is effective in reducing disease progression. Eprosartan also has sympathoinhibitory activity, as demonstrated by an inhibition of the pressor responses induced by activation of sympathetic outflow through spinal cord stimulation in pithed rats. In contrast, some of the other angiotensin II receptor antagonists, such as losartan, at equivalent angiotensin II blocking doses, have no effect on sympathetic nervous system activity. Because eprosartan can inhibit both the direct effects of angiotensin II as well as the indirect effects that are mediated by enhanced sympathetic neurotransmission, this may represent an important advance in the treatment of elevated systolic blood pressure.

Although these agents /angiotensin II receptor antagonists/ are similar to ACE inhibitors in that they decrease the effects of angiotensin II, rather than decreasing the formation of angiotensin II, drugs antagonize angiotensin II at the type I angiotensin receptor. This allows the drugs to inhibit the vasoconstrictive and aldosterone promoting effects of angiotensin II without interfering with bradykinin degradation, significantly reducing the adverse effects of cough and angioedema seen with ACE inhibitor therapy. ... /Angiotensin II receptor antagonists/

The terminal elimination half-life of eprosartan following oral administration is typically 5 to 9 hours.

... The mean terminal elimination half-life of eprosartan following multiple oral doses of 600 mg was approximately 20 hours. ...

After oral administration of eprosartan to healthy volunteers ... the drug's terminal elimination half-life is typically 5-9 hours after oral administration. ...

Eprosartan is not metabolized by the cytochrome P450 system. It is mainly eliminated as unchanged drug. Less than 2% of an oral dose is excreted in the urine as a glucuronide.

Following an oral dose of (14)C eprosartan, about 90% is recovered in the feces and about 7% in the urine. Approximately 20% of the radioactivity excreted in the urine was an acyl glucuronide of eprosartan with the remaining 80% being unchanged eprosartan.

2KH13Z0S0Y

EPROSARTAN

Mechanisms of Action [MoA] - Angiotensin 2 Receptor Antagonists

Established Pharmacologic Class [EPC] - Angiotensin 2 Receptor Blocker

Eprosartan is an Angiotensin 2 Receptor Blocker. The mechanism of action of eprosartan is as an Angiotensin 2 Receptor Antagonist.

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.

Agents that antagonize the ANGIOTENSIN II TYPE 2 RECEPTOR.

Absolute bioavailability following a single 300 mg oral dose of eprosartan is approximately 13%. Administering eprosartan with food delays absorption.

Eprosartan is excreted in animal milk; it is not known whether eprosartan is excreted in human milk.

Plasma protein binding of eprosartan is high (approximately 98%) and constant over the concentration range achieved with therapeutic doses. The pooled population pharmacokinetic analysis from two Phase 3 trials of 299 men and 172 women with mild to moderate hypertension (aged 20 to 93 years) showed that eprosartan exhibited a population mean oral clearance (CL/F) for an average 60-year-old patient of 48.5 L/hr. The population mean steady-state volume of distribution (Vss/F) was 308 L. Eprosartan pharmacokinetics were not influenced by weight, race, gender or severity of hypertension at baseline. Oral clearance was shown to be a linear function of age with CL/F decreasing 0.62 L/hr for every year increase.

Eprosartan is eliminated by biliary and renal excretion, primarily as unchanged compound. Less than 2% of an oral dose is excreted in the urine as a glucuronide. There are no active metabolites following oral and intravenous dosing with (14)C eprosartan in human subjects. Eprosartan was the only drug-related compound found in the plasma and feces. Following intravenous (14)C eprosartan, about 61% of the material is recovered in the feces and about 37% in the urine. Following an oral dose of (14)C eprosartan, about 90% is recovered in the feces and about 7% in the urine.

Absolute bioavailability following a single 300 mg oral dose of eprosartan is approximately 13%. Eprosartan plasma concentrations peak at 1 to 2 hours after an oral dose in the fasted state. Administering eprosartan with food delays absorption, and causes variable changes (<25%) in Cmax and AUC values which do not appear clinically important. Plasma concentrations of eprosartan increase in a slightly less than dose-proportional manner over the 100 mg to 800 mg dose range. The mean terminal elimination half-life of eprosartan following multiple oral doses of 600 mg was approximately 20 hours. Eprosartan does not significantly accumulate with chronic use.

For more Absorption, Distribution and Excretion (Complete) data for EPROSARTAN (6 total), please visit the HSDB record page.

MEDICATION

Angiotensin II Type 2 Receptor Blockers; Antihypertensive Agents

Use (kg) in Switzerland (2009): >1000

Preparation: J. A. Finkelstein et al., European Patent Office patent 403159 (1990 to SmithKline Beckman); eidem, United States of America patent 5185351 (1993 to SmithKline Beecham).

Methyl 4-(bromomethyl)benzoate and 5-chloro-2-propylimidazole are condensed using potassium carbonate in DMF to give the 1-(4-methoxycarbonyl)benzyl derivative of the imidazole (I). I, with the monomethyl ester of 2-thenylmalonate, in a solution of piperidine and pyridine in toluene forms the dimethyl ester of eprosartan, which is saponified to the diacid. The mesylate salt is obtained with methanesulfonic acid. /Eprosartan mesylate/

Table: Eprosartan Mesylate Preparations [Table#7218]

Table: Eprosartan Mesylate Combination Preparations [Table#7219]