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Several angiotensin II receptor blockers (ARB) are currently available for the treatment of hypertension. These drugs share a common mechanism of action-antagonism of angiotensin II AT1 receptors; however, their receptor binding kinetics differ. Candesartan has a higher affinity for the AT1 receptor than all the other ARB. In addition, candesartan and irbesartan block the AT1 receptor with insurmountable antagonism, whereas losartan, valsartan, and eprosartan are competitive antagonists. The pharmacokinetics of these ARB also differ in terms of oral bioavailability, rate of absorption, metabolism, and route and rate of elimination. Both losartan potassium and candesartan cilexetil are prodrugs; however, losartan is partially converted into EXP3174 in the liver, whereas candesartan cilexetil is converted completely into candesartan during gastrointestinal absorption. On the basis of elimination half-lives, losartan, valsartan, and eprosartan may be classified as shorter acting and candesartan cilexetil and irbesartan as longer acting. Each drug effectively lowers blood pressure during once daily administration to patients with mild to moderate hypertension, with candesartan cilexetil requiring the lowest dosage and providing dose-dependent efficacy. Initial comparative clinical trials suggest that both candesartan cilexetil and irbesartan in the doses used are significantly more effective than losartan in lowering trough sitting diastolic blood pressure. It remains to be determined, however, whether the observed pharmacologic and pharmacokinetic differences among the members of the ARB class will have a clinically significant impact on long-term cardiovascular outcomes and reductions of cardiovascular mortality.

Newly emerging pharmacologic differences in angiotensin II receptor blockers