The comparative pharmacology of angiotensin II receptor antagonists

Abstract

Several orally active non-peptide angiotensin II subtype 1 (AT1) receptor antagonists are now available for the treatment of hypertension. These agents have a common mechanism of action--blockade of the binding of angiotensin II to the subtype 1 receptor--and their binding to this receptor is generally insurmountable. There are some pharmacokinetic and pharmacodynamic differences between these antagonists, which may reflect in their clinical efficacy, especially at the end of the dosing interval. Losartan has an active metabolite that prolongs its duration of action, and candesartan cilexetil requires conversion to an active form after administration. Telmisartan has the longest duration of action, with a terminal elimination half-life of around 24 h in comparison with 11-15 h for irbesartan, the agent with the next longest half-life. The long duration of action and insurmountable binding to the receptor may be related to the slow dissociation kinetics of the antagonists from the AT1 receptor. Comparative clinical studies suggest that at the recommended dose losartan, the original drug in this class, has a lower antihypertensive efficacy than the newer agents, such as telmisartan. It is possible that these differences between angiotensin II receptor antagonists are due to variations in the degree and duration of receptor blockade, and may be of clinical significance with regard to the cardioprotective and renoprotective effects of this class of antihypertensive agents.