AT1/angiotensin II type 1 receptor (IC50 = 9.2 nM)

In intact RVSMC cell and membrane preparations, telmisartan inhibits 125I-AngII binding to the AT1 receptor in a concentration-dependent manner with an IC50 of 9.2 ± 0.8 nM. The IC50 value was 2.9 ± 0.5 nM when angiotensin II took the place of 125I-AngII under the same experimental circumstances. Unlabeled Telmisartan and cold AngII, with IC50 values of 7.7 ± 1.8 nM and 32.7 ± 5.7 nM, respectively, replaced the specific binding of [3H]Telmisartan to SMC membranes [1]. Treatment with telmisartan (100 μM) inhibits the growth of three EAC cell lines (OE19, OE33, and SKGT-4), causes cell cycle arrest in G0/G1 phase, controls proteins related to the cell cycle in EAC cells, and activates AMPK and mTOR pathway in cells. RTKs, downstream effectors, and cell cycle-related proteins are all inhibited by telmisartan [5].

The specific binding of [3H]Telmisartan to the surface of live RVSMC was saturated and increased quickly to approach equilibrium within 1 hour in rats treated with Telmisartan (0.1, 0.3, and 1 mg/kg). With a dissociation half-life (t1/2) of 75 minutes, telmisartan dissociates from the receptor very slowly—nearly five times slower than angiotensin II (AngII) and comparable to candesartan. Telmisartan reduces the blood pressure response to exogenous AngII in vivo in a dose-dependent manner [1]. Regardless of whether therapy was started prior to or following aneurysm formation, or if it was continued for a brief or prolonged duration, telmisartan (10 mg/kg/day) was also successful in preventing aneurysm pathogenesis following PPE infusion. In aneurysmal aortas, telmisartan treatment was linked to lower messenger RNA levels of CCL5 and matrix metalloproteinases 2 and 9, but it had no discernible impact on the expression of genes controlled by PPARγ [2]. In 5XFAD animals, telmisartan (1 mg/kg/day) dramatically reduced neuron loss and spatial acquisition impairment, although NeuN expression in the hippocampus remained unchanged. 5XFAD mice's brains had less amyloid and microglia buildup when treated with telmisartan (1 mg/kg/day), which also causes microglia to polarize toward a neuroprotective phenotype. However, 5XFAD mice remain the same. NEP and IDE expression levels in particular brain areas [3]. Rats' immobility time is greatly reduced by telmisartan (0.05, 0.1, 1 mg/kg, po), which also adversely affects sadness and anxiety in addition to significantly lowering rats' blood cortisol, NO, IL-6, and IL-1β [4]. In mice bearing xenografts produced from OE19 cells, telmisartan (50 μg, ip) lowers tumor growth by 73.2%. Furthermore, the expression of miRNA was considerably changed in vivo by telmisartan [5].

In this study, researchers investigated the molecular basis of telmisartan's insurmountable antagonism in vitro, and the effect of telmisartan has been compared in vivo with that of irbesartan and candesartan. Association and dissociation kinetics of telmisartan to AT1 receptors have been characterized in vitro on rat vascular smooth muscle cells (RVSMC) expressing solely the AT1 receptor subtype. In a second set of experiments, the antagonistic efficacy of single intravenous doses (0.1, 0.3, and 1 mg/kg) of telmisartan was compared with that of irbesartan (0.3, 1.0, 3.0, and 10.0 mg/kg) and candesartan (0.3 and 1 mg/kg) in conscious, normotensive, male Wistar rats. The results show that the specific binding of [(3)H]telmisartan to the surface of living RVSMC is saturable and increases quickly to reach equilibrium within 1 h. Telmisartan dissociates very slowly from the receptor with a dissociation half-life (t(1/2)) of 75 min, which is comparable with candesartan and almost 5 times slower than angiotensin II (AngII). In vivo, telmisartan blunts the blood pressure response to exogenous AngII dose dependently. The blockade is long lasting and remains significant at 24 h at doses >0.1 mg/kg. Ex vivo assessment of the AT1 receptor blockade using an in vitro AngII receptor binding assay shows similar results. When administered intravenously in rats, telmisartan is 10-fold more potent than irbesartan and comparable to candesartan. Taken together, our in vitro data show that the insurmountable antagonism of telmisartan is due at least in part to its very slow dissociation from AT1 receptors.

Cell proliferation was assayed using the CCK-8 cell counting kit according to the manufacturer's instructions. Briefly, 5 × 103 cells were seeded into each well of a 96-well plate and cultured in 100 μL of RPMI-1640 supplemented with 10% FBS. After 24 h, ARBs (telmisartan, irbesartan, losartan, and valsartan at 0, 1, 10, or 100 μM) or vehicle was added to each well, and cells were cultured for an additional 48 h. CCK-8 reagent (10 μL) was added to each well, and the plates were incubated at 37°C for 3 h. The absorbance was measured at 450 nm using a microplate reader.[5]

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Cell cycle and apoptosis analysis[5]
Cell cycle profiles were analyzed after telmisartan treatment to assess growth inhibition. OE19, OE33, and SKGT-4 cells (1.0 × 106 cells in a 100 mm diameter dish) were treated with or without 100 μM telmisartan for 24–48 h. Cell cycle progression was analyzed by measuring the amount of propidium iodide (PI)-labeled DNA in ethanol-fixed cells. The fixed cells were washed with PBS and then stored at −20°C for flow cytometry analysis. On the day of analysis, the cells were washed with cold PBS, suspended in 100 μL of PBS with 10 μL of RNase A (250 μg/mL) and incubated for 30 min. A 110 μL aliquot of PI (100 μg/mL) was added to each suspension, and the cells were incubated at 4°C for at least 30 min prior to analysis. Apoptotic and necrotic cell death was analyzed by double staining with FITC-conjugated Annexin V and PI, which is based on the binding of Annexin V to apoptotic cells with exposed phosphatidylserine and PI labeling of late apoptotic/necrotic cells with membrane damage. Tumor cells were treated for 24 and 48 h. Staining was performed according to the manufacturer's instructions. Flow cytometry was performed using a Cytomics FC 500 flow cytometer. Cell percentages were determined using Kaluza software. All experiments were performed in triplicate.

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Telmisartan with partial activation of peroxisome proliferator-activated receptor γ (PPARγ) powerfully reduces blood pressure, improves endothelial function and lipid metabolism. Hepatocyte growth factor/mesenchymal-epithelial transition factor (HGF/Met) system in the local vasculature plays a pivotal role in maintaining normal endothelial function. This study is aimed to evaluate whether telmisartan directly prevents angiotensin II (Ang II)-induced endothelial dysfunction (ED) via activating HGF/Met system and/or PPARγ pathway. The isolated aortic rings of rabbits were incubated with Ang II (0.01-1 μM), telmisartan (0.1-10 μM), SU11274 (5 μM) as a specific Met inhibitor, GW9662 (10 μM) as a PPARγ antagonist alone or a combination for 6 h. Ang II obviously inhibited the mRNA and protein expression of HGF, Met and PPARγ, and the accumulative concentration-relaxation of the aortic rings to acetylcholine, among which the inhibitory effect of 1 μM Ang II was most significant. By contrast, telmisartan significantly increased the mRNA and protein expression of HGF, Met, and PPARγ, thus preventing Ang II-induced ED in a dose-dependent pattern. However, SU11274, GW9662 or a combination of both partially abolished the protective effects derived from telmisartan, with the effect of SU11274 exceeding that of GW9662. These results demonstrate that Ang II-induced ED in rabbit aortic rings in vitro can be prevented by telmisartan through selective PPARγ-modulating pathway. Moreover, this study indicates for the first time that activating HGF/Met system in the local vasculature is involved in the protective mechanism of telmisartan.[2]

Male athymic mice (BALB/c-nu/nu; 6 weeks old; 20–25 g) were maintained under specific pathogen-free conditions using a laminar airflow rack. The mice had continuous free access to sterilized (γ-irradiated) food and autoclaved water. Each mouse was subcutaneously inoculated with OE19 cells (5 × 10~6 cells per animal) in the flank. One week later, the xenografts were identifiable as masses with a maximal diameter > 4 mm. The animals were randomly assigned to treatment with telmisartan (50 μg per day) or diluent only (control). The telmisartan group was intraperitoneally (i.p.) injected five times per week with 2 mg/kg telmisartan for four weeks; the control group was administered 5% DMSO alone for four weeks. Tumor growth was monitored daily by the same investigators (S. Fujihara and A. Morishita), and tumor size was measured weekly. The tumor volume (mm3) was calculated as the tumor length (mm) × tumor width (mm)2/2. All animals were sacrificed on day 22 after treatment, and all animals survived during this period. Between-group differences in tumor growth were analyzed by two-way ANOVA.[5]

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The renin-angiotensin system (RAS) is a major circulative system engaged in homeostasis modulation. Angiotensin II (Ang II) serves as its main effector hormone upon binding to its primary receptor, Ang II receptor type 1 (AT1R). It is well established that an intrinsic independent brain RAS exists. Abnormal AT1R activation both in the periphery and in the brain probably contributes to the development of Alzheimer's disease (AD) pathology that is characterized, among others, by brain inflammation. Moreover, treatment with drugs that block AT1R (AT1R blockers, ARBs) ameliorates most of the clinical risk factors leading to AD. Previously we showed that short period of intranasal treatment with telmisartan (a brain penetrating ARB) reduced brain inflammation and ameliorated amyloid burden (a component of Alzheimer's plaques) in AD transgenic mouse model. In the present study, we aimed to examine the long-term effect of intranasally administrated telmisartan on brain inflammation features including microglial activation, astrogliosis, neuronal loss and hippocampus-dependent cognition in five-familial AD mouse model (5XFAD). Five month of intranasal treatment with telmisartan significantly reduced amyloid burden in the cortex and hippocampus of 5XFAD mice as compared with the vehicle-treated 5XFAD group. Similar effects were also observed for CD11b staining, which is a marker for microglial accumulation. Telmisartan also significantly reduced astrogliosis and neuronal loss in the cortex of 5XFAD mice compared with the vehicle-treated group. Improved spatial acquisition of the 5XFAD mice following long-term intranasal administration of telmisartan was also observed. Taken together, our data suggest a significant role for AT1R blockage in mediating neuronal loss and cognitive behavior, possibly through regulation of amyloid burden and glial inflammation.[3]

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Background: Role of brain renin angiotensin system (RAS) is well understood and various clinical studies have proposed neuroprotective effects of ARB's. It is also assumed that diabetic depression is associated with activation of brain RAS, HPA axis dysregulation and brain inflammatory events. Therefore, the present study was designed to investigate the antidepressant effect of low dose telmisartan (TMS) in diabetes induced depression (DID) in rats.[4]
Methods: Diabetes was induced by injecting streptozotocin. After 21days of treatment the rats were subjected to forced swim test (FST). The rats, with increased immobility time, were considered depressed and were treated with vehicle or TMS (0.05mg/kg, po) or metformin (200mg/kg, po) or fluoxetine (20mg/kg, po). A separate group was also maintained to study the combination of metformin and TMS. At the end of 21days of treatments, FST, open field test (OFT) and elevated plus maze (EPM) paradigm were performed. Blood was drawn to estimate serum cortisol, nitric oxide (NO), interleukin-6 (IL-6) and interleukin-1β (IL-1β).[4]
Results: Persistent hyperglycemia resulted in depression and anxiety in rats as observed by increased immobility, reduced latency for immobility, reduced open arm entries and time spent. The depressed rats showed a significant rise in serum cortisol, NO, IL-6 and IL-1β (p<0.001). TMS antagonized depression and anxiety. It also significantly attenuated serum cortisol, NO, IL-6 and IL-1β (p<0.001).[4]
Conclusions: Low dose TMS and its combination with metformin normalizes depressive mood, reduces pro-inflammatory mediators and ameliorates the HPA axis function; thereby providing beneficial effects in DID.

Absorption, Distribution and Excretion
Oral telmisartan follows nonlinear pharmacokinetics over the dose range of 20 mg to 160 mg. Both Cmax and AUC present greater than proportional increases at higher doses. With once-daily dosing, telmisartan has trough plasma concentrations of about 10% to 25% of peak plasma concentrations. The absolute bioavailability of telmisartan depends on the dosage. At 40 mg and 160 mg, the bioavailability was 42% and 58%, respectively. Food slightly decreases bioavailability. For instance, when the 40 mg dose is administered with food, a decrease of about 6% is seen, and with the 160 mg dose, there is a decrease of about 20%.
Following either intravenous or oral administration of 14C-labeled telmisartan, most of the administered dose (>97%) was eliminated unchanged in feces via biliary excretion; only minute amounts were found in the urine (0.91% and 0.49% of total radioactivity, respectively).
Telmisartan has a volume of distribution of approximately 500 liters.
Telmisartan has a total plasma clearance of >800 mL/min.
Following either intravenous or oral administration of (14)C-labeled telmisartan, most of the administered dose (>97%) was eliminated unchanged in feces via biliary excretion; only minute amounts were found in the urine (0.91% and 0.49% of total radioactivity, respectively).
Following oral administration, peak concentrations (Cmax) of telmisartan are reached in 0.5 to 1 hour after dosing. Food slightly reduces the bioavailability of telmisartan, with a reduction in the area under the plasma concentration-time curve (AUC) of about 6% with the 40 mg tablet and about 20% after a 160 mg dose. The absolute bioavailability of telmisartan is dose dependent. At 40 and 160 mg the bioavailability was 42% and 58%, respectively. The pharmacokinetics of orally administered telmisartan are nonlinear over the dose range 20 to 160 mg, with greater than proportional increases of plasma concentrations (Cmax and AUC) with increasing doses. Telmisartan shows bi-exponential decay kinetics with a terminal elimination half life of approximately 24 hours. Trough plasma concentrations of telmisartan with once daily dosing are about 10% to 25% of peak plasma concentrations. Telmisartan has an accumulation index in plasma of 1.5 to 2.0 upon repeated once daily dosing.
Telmisartan is highly bound to plasma proteins (>99.5%), mainly albumin and a1 - acid glycoprotein. Plasma protein binding is constant over the concentration range achieved with recommended doses. The volume of distribution for telmisartan is approximately 500 liters indicating additional tissue binding.
It is not known whether telmisartan is excreted in human milk, but telmisartan was shown to be present in the milk of lactating rats.
To study the pharmacolkinetics of telmisartan in healthy Chinese male subjects after oral administration of two dosage levels, 36 healthy subjects were divided into two groups and given a single oral dose of 40 or 80 mg telmisartan (CAS 144701-48-4, MicardisPlus). A sensitive liquid chromatography-tandem mass spectrometry method (LC-MS-MS) was used for the determination of telmisartan in plasma. Both, a non-compartmental and compartmental method were used for analysis of parameters of kinetics. The main pharmacokinetic parameters of the 40 mg and 80 mg regimen group were as follows: t(max) (1.76 +/- 1.75) h, (1.56 +/- 1.09) h, C(max) (163.2 +/- 128.4) ng/mL, (905.7 +/- 583.4) ng/mL, t1/2 (23.6 +/- 10.8) h, (23.0 +/- 6.4) h, AUC(o-t) (1456 +/- 1072) ng x h/mL, (6759 +/- 3754) ng x h/mL, AUC(o-infinity (1611 +/- 1180) ng x h/mL, (7588 +/- 4661) ng x h/mL, respectively. After dose normalization, there was significant difference for main pharmacokinetic parameters C(max) AUC(o-t) and AUC(o-infinity) between two dosage level groups. The plasma concentration-time profile of telmisartan was characterized by a high degree of inter-individual variability and the disposition of telmisartan in healthy Chinese subjects was dose-dependent. The pharmacokinetic parameters C(max) and AUC(o-inifinity) of the 80 mg regimen group increased to about 5-fold compared to that of the 40 mg regimen group, but there was no significant difference for t(max) and t1/2 between the two dose groups.

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Metabolism / Metabolites
Minimally metabolized by conjugation to form a pharmacologically inactive acyl-glucuronide, the glucuronide of the parent compound is the only metabolite that has been identified in human plasma and urine. The cytochrome P450 isoenzymes are not involved in the metabolism of telmisartan.
Telmisartan is metabolized by conjugation to form a pharmacologically inactive acyl glucuronide; the glucuronide of the parent compound is the only metabolite that has been identified in human plasma and urine. After a single dose, the glucuronide represents approximately 11% of the measured radioactivity in plasma. The cytochrome P450 isoenzymes are not involved in the metabolism of telmisartan.

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Biological Half-Life
Telmisartan displays bi-exponential decay kinetics with a terminal elimination half-life of approximately 24 hours.
Telmisartan shows bi-exponential decay kinetics with a terminal elimination half life of approximately 24 hours.

Toxicity Summary
IDENTIFICATION AND USE: Telmisartan is a white to slightly yellowish solid that is formulated into oral tablets. Telmisartan is an angiotensin II type 1 (AT1) receptor antagonist. It is used alone or in combination with other classes of antihypertensive in the management of hypertension. It is also indicated for reduction of the risk of myocardial infarction, stroke, or death from cardiovascular causes in patients 55 years of age or older at high risk of developing major cardiovascular events who are unable to take ACE inhibitors. HUMAN EXPOSURE AND TOXICITY: The most likely manifestations of telmisartan overdose include hypotension, dizziness and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. The use of telmisartan 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 telmisartan. ANIMAL STUDIES: Telmisartan was not carcinogenic when administered by dietary administration to mice and rats for up to 2 years. Also, the fertility of male and female rats was unaffected by administration of the drug. No teratogenic effects were observed when telmisartan was administered to pregnant rats at oral doses as high as 50 mg/kg/day or pregnant rabbits at oral doses as high as 45 mg/kg/day. However, in rabbits, embryolethality associated with maternal toxicity (reduced body weight gain and food consumption) was observed. In rats, the maternally toxic dose was 15 mg/kg/day. When this dose was administered during late gestation and lactation it produced adverse effects in neonates, including reduced viability, low birth weight, delayed maturation, and decreased weight gain. Genotoxicity assays did not reveal any drug-related effects at either the gene or chromosome level. These assays included bacterial mutagenicity tests with Salmonella and E. coli (Ames test), a gene mutation test with Chinese hamster V79 cells, a cytogenetic test with human lymphocytes, and a mouse micronucleus test.

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Hepatotoxicity
Telmisartan has been associated with a low rate of serum aminotransferase elevations (
Likelihood score: E* (Unproved but suspected rare cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the use of telmisartan during breastfeeding and the manufacturer advises avoidance of breastfeeding during telmisartan therapy. An alternate drug may be preferred, especially while nursing a newborn or preterm infant.
◉ 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.

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Protein Binding
Telmisartan is highly bound to plasma proteins (>99.5%), mainly albumin and alpha 1-acid glycoprotein. Binding is not dose-dependent.

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Interactions
In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of non-steroidal anti-inflammatory agents (NSAIDs), including selective selective cyclooxygenase-2 (COX-2) inhibitors, with angiotensin II receptor antagonists, including telmisartan, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving telmisartan and NSAID therapy. The antihypertensive effect of angiotensin II receptor antagonists, including telmisartan may be attenuated by NSAIDs including selective COX-2 inhibitors.
Do not co-administer aliskiren with Micardis in patients with diabetes. Avoid use of aliskiren with Micardis in patients with renal impairment (GFR <60 mL/min).
Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists including Micardis. Therefore, monitor serum lithium levels during concomitant use.
Co-administration of telmisartan 80 mg once daily and ramipril 10 mg once daily to healthy subjects increases steady-state Cmax and AUC of ramipril 2.3- and 2.1-fold, respectively, and Cmax and AUC of ramiprilat 2.4- and 1.5-fold, respectively. In contrast, Cmax and AUC of telmisartan decrease by 31% and 16%, respectively. When co-administering telmisartan and ramipril, the response may be greater because of the possibly additive pharmacodynamic effects of the combined drugs, and also because of the increased exposure to ramipril and ramiprilat in the presence of telmisartan. Concomitant use of Micardis and ramipril is not recommended.
For more Interactions (Complete) data for TELMISARTAN (6 total), please visit the HSDB record page.

[1]. In vitro and in vivo characterization of the activity of telmisartan: an insurmountable angiotensin II receptor antagonist. J Pharmacol Exp Ther. 2002 Sep;302(3):1089-95.

[2]. Inhibition or deletion of angiotensin II type 1 receptor suppresses elastase-induced experimental abdominal aortic aneurysms. J Vasc Surg. 2017 Apr 20. pii: S0741-5214(17)30100-3.

[3]. Intranasal telmisartan ameliorates brain pathology in five familial Alzheimer's disease mice. Brain Behav Immun. 2017 Apr 3.

[4]. Telmisartan attenuates diabetes induced depression in rats. Pharmacol Rep. 2017 Apr;69(2):358-364.

[5]. The angiotensin II type 1 receptor antagonist telmisartan inhibits cell proliferation and tumor growth of esophageal adenocarcinoma via the AMPKα/mTOR pathway in vitro and in vivo. Oncotarget. 2017 Jan 31;8(5):8536-8549.

Therapeutic Uses
Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents
Micardis is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. ... Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. /Micardis/ may be used alone or in combination with other antihypertensive agents /Included in US product labeling/
Micardis is indicated for reduction of the risk of myocardial infarction, stroke, or death from cardiovascular causes in patients 55 years of age or older at high risk of developing major cardiovascular events who are unable to take ACE inhibitors. High risk for cardiovascular events can be evidenced by a history of coronary artery disease, peripheral arterial disease, stroke, transient ischemic attack, or high-risk diabetes (insulin-dependent or non-insulin dependent) with evidence of end-organ damage. Micardis can be used in addition to other needed treatment (such as antihypertensive, antiplatelet or lipid-lowering therapy). Studies of telmisartan in this setting do not exclude the possibility that telmisartan may not preserve a meaningful fraction of the effect of the ACE inhibitor to which it was compared. Consider using the ACE inhibitor first, and, if it is stopped for cough only, consider re-trying the ACE inhibitor after the cough resolves. /Included in US product label/
Both angiotensin II receptor antagonists /including telmisartan/ and ACE inhibitors have been shown to slow the rate of progression of renal disease in hypertensive patients with diabetes mellitus and microalbuminuria or overt nephropathy, and use of a drug from either class is recommended in such patients. /NOT included in US product label/
For more Therapeutic Uses (Complete) data for TELMISARTAN (8 total), please visit the HSDB record page.

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Drug Warnings
/BOXED WARNING/ WARNING: FETAL TOXICITY. When pregnancy is detected, discontinue Micardis as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus.
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 Micardis as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus. In the unusual case that there is no appropriate alternative to therapy with drugs affecting the reninangiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue Micardis, unless it is considered lifesaving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury.
Neonates with a history of in utero exposure to Micardis: If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function.
FDA Pregnancy Risk Category: D /POSITIVE EVIDENCE OF RISK. Studies in humans, or investigational or post-marketing data, have demonstrated fetal risk. Nevertheless, potential benefits from the use of the drug may outweigh the potential risk. For example, the drug may be acceptable if needed in a life-threatening situation or serious disease for which safer drugs cannot be used or are ineffective./
For more Drug Warnings (Complete) data for TELMISARTAN (17 total), please visit the HSDB record page.

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Pharmacodynamics
Telmisartan is an orally active nonpeptide angiotensin II antagonist that acts on the AT₁ receptor subtype. It has the highest affinity for the AT₁ receptor among commercially available ARBs and has minimal affinity for the AT₂ receptor. New studies suggest that telmisartan may also have PPARγ agonistic properties that could potentially confer beneficial metabolic effects, as PPARγ is a nuclear receptor that regulates specific gene transcription, and whose target genes are involved in the regulation of glucose and lipid metabolism, as well as anti-inflammatory responses. This observation is currently being explored in clinical trials. Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Telmisartan works by blocking the vasoconstrictor and aldosterone secretory effects of angiotensin II.

C33H30N4O2

514.62

514.236

C, 77.02; H, 5.88; N, 10.89; O, 6.22

144701-48-4

Telmisartan-d3;1189889-44-8;Telmisartan-d7;1794754-60-1;Telmisartan-d4;Telmisartan-13C,d3;1261396-33-1; 144701-48-4; 528560-93-2 (methyl ester)

65999

White to off-white solid powder

1.2±0.1 g/cm3

771.9±70.0 °C at 760 mmHg

261-263°C

420.6±35.7 °C

0.0±2.8 mmHg at 25°C

1.667

7.73

1

4

7

39

831

0

O=C(C1=CC=CC=C1C2=CC=C(CN3C4=CC(C5=NC6=CC=CC=C6N5C)=CC(C)=C4N=C3CCC)C=C2)OC

RMMXLENWKUUMAY-UHFFFAOYSA-N

InChI=1S/C33H30N4O2/c1-4-9-30-35-31-21(2)18-24(32-34-27-12-7-8-13-28(27)36(32)3)19-29(31)37(30)20-22-14-16-23(17-15-22)25-10-5-6-11-26(25)33(38)39/h5-8,10-19H,4,9,20H2,1-3H3,(H,38,39)

4-((1,7-dimethyl-2-propyl-1H,3H-[2,5-bibenzo[d]imidazol]-3-yl)methyl)-[1,1-biphenyl]-2-carboxylic 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)

Solubility in Formulation 1: ≥ 0.67 mg/mL (1.30 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 6.7 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.

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Solubility in Formulation 2: ≥ 0.67 mg/mL (1.30 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 6.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 3: 3 mg/mL (5.83 mM) in 0.5% CMC-Na/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 4: 3.33 mg/mL (6.47 mM) in 17% Polyethylene glycol 12-hydroxystearate in Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with heating and sonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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