Translations:Discovery and development of angiotensin receptor blockers/40/en

ARBs have a large therapeutic index and therefore their (mostly low) oral bioavailability does not appear to be of clinical significance. As can be seen in table 1, these drugs are highly plasma protein-bound and therefore oral administration once a day should provide sufficient antihypertensive effects. Around 14% of orally ingested losartan is metabolized to its 5-carboxylic acid metabolite EXP 3174. As mentioned before, candesartan cilexetil and olmesartan medoxomil are inactive ester prodrugs that are completely hydrolyzed to their active forms by esterases during absorption from the gastrointestinal tract. These three metabolites are more potent AT₁ receptor antagonists than their prodrugs. The other ARBs do not have active metabolites.