The new oral angiotensin II antagonist olmesartan medoxomil: a concise overview

Abstract

The new orally active angiotensin II (A II) type-1 receptor antagonist olmesartan medoxomil is a prodrug, which is rapidly converted in vivo to the active metabolite, olmesartan. The pharmacology, antihypertensive efficacy and safety of olmesartan medoxomil and/or the pharmacologically active metabolite, olmesartan, have been evaluated in both non-clinical and clinical models. Orally administered olmesartan medoxomil is rapidly absorbed from the gastrointestinal tract and converted during absorption to olmesartan, which is subsequently excreted without further metabolism. Peak plasma concentrations of olmesartan occur 1-3 h after administration, after which concentrations decrease with an elimination half-life of 10-15 h. The absolute bioavailability of olmesartan from olmesartan medoxomil tablets is 28.6%. In a single-dose crossover study in 16 patients with mild-to-moderate hypertension receiving a sodium-restricted diet, statistically significant lowering

Antihypertensive efficacy of olmesartan compared with other antihypertensive drugs

“…The comparative studies demonstrated that, in patients with moderate-to-severe hypertension, olmesartan medoxomil (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) 1,7 Even at these lower doses, however, olmesartan maintained efficacy similar or superior to that of the comparators. In the studies comparing olmesartan with captopril and losartan, fewer patients were titrated to higher doses of olmesartan than in the case of either captopril or losartan.…”

“…Olmesartan medoxomil is neither a substrate for, nor an inhibitor or inducer of, cytochrome P-450 isoforms. 7,8 This property, along with other general pharmacokinetic properties, limits the risk of pharmacokinetic interactions between olmesartan once daily (o.d.) and other co-administered drugs.…”

“…and other co-administered drugs. 7,8 The therapeutic profile of olmesartan has been compared with those of four commonly used antihypertensives during the pre-launch clinical development phase of this novel A II receptor blocker. One study compared the efficacy of olmesartan with that of the ␤-adrenoceptor blocker atenolol (plus hydrochlorothiazide (HCTZ) background therapy) in patients with moderate-to-severe hypertension.…”

Immunostimulation in the era of the metagenome

“…It should be noted that olmesartan is considered a very safe drug, [80][81][82][83] for which the US FDA has not dictated any unsafe dosing level. However, there are definite sequelae that some might consider to be 'adverse events'-autoimmune patients initiating this therapy appear to experience immunopathology, sometimes severe immunopathology.…”

RP-HPLC-DAD method for determination of olmesartan medoxomil in bulk and tablets exposed to forced conditions

“…1a) is a prodrug and rapidly hydrolyzes in plasma during absorption to form its active metabolite olmesartan (Fig. 1b) (3)(4)(5). It is a selective AT1 subtype angiotensin II receptor blocker (6,7), which was recently approved by the US-FDA (8) to treat patients with hypertension.…”