|Metabolism||Minimal hepatic (glucuronidation)|
|Biological half-life||24 hours|
|Chemical and physical data|
|Molar mass||514.617 g/mol|
|3D model (JSmol)|
Telmisartan (INN) // is an angiotensin II receptor antagonist (angiotensin receptor blocker, ARB) used in the management of hypertension. It was discovered by Boehringer Ingelheim and launched in 1999 as Micardis.
Telmisartan is contraindicated during pregnancy. Like other drugs affecting the renin–angiotensin system (RAS), telmisartan can cause birth defects, stillbirths, and neonatal deaths. It is not known whether the drug passes into the breast milk. Also it is contraindicated in bilateral renal artery stenosis in which it can cause renal failure.
Side effects are similar to other angiotensin II receptor antagonists and include tachycardia and bradycardia (fast or slow heartbeat), hypotension (low blood pressure), edema (swelling of arms, legs, lips, tongue, or throat, the latter leading to breathing problems), and allergic reactions.
Due to its mechanism of action, telmisartan increases blood potassium levels. Combination with potassium preparations or potassium-sparing diuretics could cause hyperkalaemia (excessive potassium levels). Combination with NSAIDs, especially in patients with impaired kidney function, has a risk of causing (usually reversible) kidney failure.
Mechanism of action
In addition to blocking the RAS, telmisartan acts as a selective modulator of peroxisome proliferator-activated receptor gamma (PPAR-γ), 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).
Telmisartan's activity at the peroxisome proliferator-activated receptor delta (PPAR-δ) receptor has prompted speculation around its potential as a sport doping agent as an alternative to GW 501516. Telmisartan activates PPAR-δ receptors in several tissues.
The substance is quickly but to varying degrees absorbed from the gut. The average bioavailability is about 50% (42–100%). Food intake has no clinically relevant influence on the kinetics of telmisartan. Plasma protein binding is over 99.5%, mainly to albumin and alpha-1-acid glycoprotein. It has the longest half-life of any ARB (24 hours) and the largest volume of distribution among ARBs (500 liters). Less than 3% of telmisartan is inactivated by glucuronidation in the liver, and over 97% is eliminated in unchanged form via bile and faeces.
The Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) was one of the largest ARB clinical studies ever undertaken; 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 hospitalization for heart failure, in high CV risk patients.
The study showed 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, in a patient population selected to tolerate ACE inhibitors, telmisartan was shown to be better tolerated and associated with higher treatment compliance than ramipril.
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 Telmisartan Randomized Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease (TRANSCEND) study. 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."
The Prevention Regimen For Effectively Avoiding Second Strokes (PRoFESS) study investigated therapy with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years. This treatment did not significantly lower the rate of recurrent stroke, major cardiovascular events, or diabetes.
Telmisartan has been found to have activity against a variety of cancers in vitro, including prostate, renal, colon, leukemia, and ovarian cancer. The mechanisms of telmisartan's anti-cancer activity have been found to include up-regulation of proliferator-activated-receptor (PPAR) pathway, Bcl-2, and caspase activation.
Diabetes type II
According to a study with 18 patients, telmisartan can replace valsartan and candesartan for hypertensive patients which have also diabetes type II because telmisartan has additional advantages of insulin sensitivity and antiatherosclerosis through probably its effects on PPAR-γ.
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- Pritor prescribing information
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- Drugs.com: Micardis
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- Clinical trial number NCT00153062 for "PRoFESS - Prevention Regimen For Effectively Avoiding Second Strokes" at ClinicalTrials.gov
- Wu, T. T.; Niu, H. S.; Chen, L. J.; Cheng, J. T.; Tong, Y. C. (2016). "Increase of human prostate cancer cell (DU145) apoptosis by telmisartan through PPAR-delta pathway". European Journal of Pharmacology. 775: 35–42. doi:10.1016/j.ejphar.2016.02.017. PMID 26852954.
- De Araújo Júnior, R. F.; Leitão Oliveira, A. L.; De Melo Silveira, R. F.; De Oliveira Rocha, H. A.; De França Cavalcanti, P; De Araújo, A. A. (2014). "Telmisartan induces apoptosis and regulates Bcl-2 in human renal cancer cells." Experimental Biology and Medicine". Experimental biology and medicine (Maywood, N.J.). 240 (1): 34–44. doi:10.1177/1535370214546267. PMC . PMID 25125501.
- Lee, L. D.; Mafura, B; Lauscher, J. C.; Seeliger, H; Kreis, M. E.; Gröne, J (2014). "Antiproliferative and apoptotic effects of telmisartan in human colon cancer cells". Oncology letters. 8 (6): 2681–2686. doi:10.3892/ol.2014.2592. PMC . PMID 25360175.
- Kozako, T; Soeda, S; Yoshimitsu, M; Arima, N; Kuroki, A; Hirata, S; Tanaka, H; Imakyure, O; Tone, N; Honda, S; Soeda, S (2016). "Angiotensin II type 1 receptor blocker telmisartan induces apoptosis and autophagy in adult T‐cell leukemia cells". FEBS open bio. 6 (5): 442–460. doi:10.1002/2211-5463.12055. PMC . PMID 27419050.
- Pu, Z; Zhu, M; Kong, F (2016). "Telmisartan prevents proliferation and promotes apoptosis of human ovarian cancer cells through upregulating PPARγ and downregulating MMP‑9 expression". Molecular Medicine Reports. 13 (1): 555–559. doi:10.3892/mmr.2015.4512. PMID 26548340.
- Yoshitaka Miura, MD, PHD, Naoki Yamamoto, MD, Shin Tsunekawa, MD, Seiko Taguchi, MD, Yoko Eguchi, MD, PHD, Nobuaki Ozaki, MD, PHD and Yutaka Oiso, MD, PHD. "Replacement of Valsartan and Candesartan by Telmisartan in Hypertensive Patients With Type 2 Diabetes". Retrieved September 20, 2016.