Telmisartan

Systematic (IUPAC) name
2-(4-{[4-methyl-6-(1-methyl-1H-1,3-benzodiazol-2-yl)-2-propyl-1H-1,3-benzodiazol-1-yl]methyl}phenyl)benzoic acid
Identifiers
CAS number	144701-48-4
ATC code	C09CA07
PubChem	CID 65999
IUPHAR ligand ID	592
DrugBank	APRD01247
Chemical data
Formula	C33H30N4O2
Mol. mass	514.617 g/mol
Pharmacokinetic data
Bioavailability	42–100%
Protein binding	=99.5%
Metabolism	Minimal hepatic
Half-life	24 hours
Excretion	Faecal 97%
Therapeutic considerations
Pregnancy cat.	D (Au), D (U.S.)
Legal status	S4 (Au), POM (UK), ?-only (U.S.)
Routes	Oral
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Telmisartan (INN) (pronounced /t?lm?'s?rt?n/) is an angiotensin II receptor antagonist (ARB) used in the management of hypertension. It is marketed under the trade names , Micardis (Boehringer Ingelheim), Targit (Pfizer India Ltd)

[edit] Administration

The usually effective dose Telmisartan ( T24 marketed by Rhys Healthcare) is 40 mg once daily. Some patients may already benefit at a daily dose of 20 mg. In cases where the target blood pressure is not achieved, telmisartan dose can be increased to a maximum of 80 mg once daily. ^[1]

[edit] Mode of action

Telmisartan (Teli marketed by cadila pharma) is an Angiotensin Receptor Blocker (ARB) that shows high affinity for the angiotensin II type 1 (AT₁) receptors, has a long duration of action, and has the longest half-life of any ARB. ^[1][2]

In addition to blocking the Renin-Angiotensin System (RAS), telmisartan acts as a selective modulator of Peroxisome proliferator-activated receptor gamma (PPAR-?), a central regulator of insulin and glucose metabolism. It is believed that telmisartan’s dual mode of action may provide protective benefits against the vascular and renal damage caused by diabetes and cardiovascular disease (CVD). ^[2]

Telmisartan has binding affinity 3000 times greater for AT₁ than AT₂ receptors. Telmisartan also has the longest half life (24 hrs) of all angiotensin II type 1 receptor antagonists.

[edit] Indication

Telmisartan is indicated in the treatment of essential hypertension. ^[1]

[edit] Key Recent Clinical Trials

[edit] ONTARGET

The ONTARGET Trial Programme (The Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) was one of the largest ARB clinical study programmes ever undertaken.^[3]

Salim Yusuf, Lead Investigator and Director of the Population Health Research Institute at McMaster University, Hamilton, Canada, presented the results of the l trial at the 57th Annual Scientific Session of the American College of Cardiology (ACC) in Chicago, USA. ^[4] The results were then published in The New England Journal of Medicine in April 2008.^[5]

25,620 patients from 733 centres in 41 countries were randomised for 5.5 years of treatment of either telmisartan, the ACE inhibitor ramipril or a combination of the two. The study aimed to investigate the role of telmisartan in Cardiovascular (CV) protection through the primary composite outcome of death from CV causes, myocardial infarction, stroke or hospilization for heart failure, in high CV risk patients.

The results revealed that telmisartan was as effective as ramipril but with lower rates of cough and angioedema which led to fewer discontinuations. The combination group experienced similar efficacy but with increased risk of hypotensive symptoms. Moreover, even in a patient population selected to tolerate ACE inhibitors, telmisartan was shown to be better tolerated and associated with higher treatment compliance than ramipril. ^[6]

[edit] TRANSCEND

As part of the ONTARGET study, patients who could not tolerate ACE inhibitors were randomly assigned to receive either telmisartan or placebo as part of the TRANSCEND (Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (CVD)) study. Results from this study were published in the Lancet, September 2008. An accompanying editorial comments: "Overall, data supporting use of angiotensin-receptor blockers to prevent vascular events in various cardiovascular groups, other than heart failure, are incomplete. TRANSCEND's results challenge the non-inferiority shown in ONTARGET and suggest no more than a modest effect, if any at all." ^[7]

[edit] PROTECTION

The PROTECTION programme (Programme of Research tO show Telmisartan End-organ proteCTION) consisted of ten trials with 6,875 patients from 32 countries.^[8]

The programme examined the efficacy of telmisartan or telmisartan/ hydrochlorothiazide at different stages of the cardiovascular and renal continuum. The trials were conducted in patients with varying degrees of cardiovascular risk from around the world

The 10 studies in the programme evaluated the effect of telmisartan on blood pressure control in two general patient populations: patients at high risk for cardiovascular disease and patients with various renal pathologies. In all the studies, telmisartan was compared either to placebo or to a gold standard medication such as the ACE inhibitors ramipril and enalapril or the ARBs losartan and valsartan.

Telmisartan met and sometimes exceeded the gold standards (ACEIs and other ARBs) during the programme. In at-risk patient populations, telmisartan induced strong and sustained blood pressure lowering throughout the critical morning period where CV risk is highest ,and renoprotective effects at every stage of the renal continuum. ^[9][10]

[edit] PRoFESS

PRoFESS - Prevention Regimen For Effectively Avoiding Second Strokes. Therapy with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke, major cardiovascular events, or diabetes. (ClinicalTrials.gov number, NCT00153062)^[11]

[edit] See also

Angiotensin Receptor Blockers: Drug discovery and development

[edit] External links

• http://www.pritor.com
• http://www.micardis.com/index.jsp
• http://www.pslgroup.com/dg/e6dce.htm
• http://www.ICMAedu.com
• http://www.emea.europa.eu

[edit] References

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Telmisartan".