Telmisartan: Standing Out in a Crowded Contest?
Author: Francesco Vittorio Costa
Source: High Blood Pressure & Cardiovascular Prevention, Volume 13, Number 3, 2006 , pp. 85-94(10)
Publisher: Adis International
Abstract:In the last 12 years, seven angiotensin II receptor blockers (angiotensin II receptor antagonists; ARBs) have been marketed. All these drugs share a common mechanism of action: they selectively block the angiotensin II subtype 1 (AT1) receptors. However, they differ in pharmacological profile, and these differences might affect their efficacy.
Among these molecules, telmisartan has a very favourable kinetic profile. It has a very long plasma half-life, a negligible renal clearance and a larger volume of distribution than other ARBs. Thus, telmisartan largely penetrates the tissue compartment, ensuring an effective blockade of the renin-angiotensin system at both the local and the systemic level. Other kinetic features of ARBs that may be relevant for their efficacy are represented by the type of drug-receptor interaction, the degree of affinity for specific receptors, and the strength and duration of receptor blockade. In this regard, when directly compared with other ARBs, telmisartan has been shown to ensure higher binding affinity and longer blockade duration to AT1 receptors than other ARBs. In addition, the very slow dissociation from AT1 receptors by telmisartan is at least in part a result of its insurmountable antagonism, resulting in a greater and longer blood pressure reduction.
Recently, it has been observed that beyond their AT1 receptor-blocking activity, some ARBs may also act as partial agonists (mixed agonist/antagonist) of peroxisome proliferator-activated receptor (PPAR)-, an intracellular regulator of lipid and glucose metabolism. Moreover, there is a growing body of evidence that activators of PPAR- exert anti-inflammatory, antioxidative and antiproliferative effects on vascular wall cells, thus decreasing the development and progression of atherosclerosis. Among ARBs, telmisartan seems to be the stronger stimulator of PPAR-. In fact, when used at the normal therapeutic dosages, other ARBs appear to have little or no effect on PPAR- activity. In this view, the available clinical data confirm that telmisartan induces favourable metabolic changes, i.e. decrease of serum glucose and triglycerides and improvement in insulin sensitivity. These changes have not been observed with other ARBs.
Thus, antihypertensive therapy based on telmisartan, in view of its very long duration of antihypertensive action, its large tissue penetration and its unique favourable metabolic effects, appears to be a very effective strategy for global cardiovascular prevention in those patients with cardiac and metabolic disorders.
Document Type: Review Article
Affiliations: Formerly Associate Professor of Clinical Pharmacology and Professor of Internal Medicine, University of Bologna, Bologna, Italy
Publication date: January 1, 2006