Treatment of hypertension with olmesartan medoxomil, alone and in combination with a diuretic: an update

Abstract

Olmesartan medoxomil is an angiotensin II (Ang II) receptor blocker (ARB) that has been approved by the US Food and Drug Administration (FDA) for the treatment of hypertension. It is a prodrug that is hydrolysed in the gut into its active metabolite, olmesartan (RNH-6270). Olmesartan is highly selective for the Ang II type 1 receptor (AT1) to which it binds completely and insurmountably and has very little affinity for the other receptor subtypes AT2 and AT4. After oral administration, in animals and humans, it achieves a maximal blood drug concentration within a maximal time of approximately 2 h. It is then slowly eliminated in the urine and faeces. His half-life is approximately 13 h, which makes it suitable for once-daily administration. Olmesartan medoxomil given orally in single daily doses of 20-40 mg has demonstrated significant blood pressure (BP) lowering effects in hypertensive patients. A medline search for the preparation of this manuscript was conducted and revealed 128 references, from 2000 to 2007. Of these, only 16 well-designed prospective clinical trials were selected. The remaining were either animal studies, reviews or studies in progress. In well-designed clinical trials, olmesartan medoxomil has demonstrated similar antihypertensive actions to the other antihypertensive drugs, as well as other members of its class given the highest recommended doses. In addition, the BP lowering effect of olmesartan, like the other members of its class, is greatly enhanced in combination with a diuretic. Its safety profile is similar to the other ARBs and no different than placebo.

Hypertension: Focus on Olmesartan Medoxomil

“…13 Chrysant et al report reductions in both systolic and diastolic blood pressure when olmesartan has been compared with placebo in many large clinical trials. 8 Unger et al also analyzed seven randomized, double blind, placebo controlled studies. These studies were large, with greater than 3000 participants, all with mild to moderate hypertension.…”

“…6 Arylesterase, located in both the intestine and plasma, rapidly converts the pro-drug olmesartan medoxomil to the active olmesartan by breakdown of the medoxomil ester. 6 Olmesartan has 100,000 times greater selectivity for the AT 1 -R than it does for the AT 2 -R 8 inhibiting the vasoconstricting and aldosterone secreting effects of Ang II while not interfering with the vasodilatory effects that occur with AT 2 -R stimulation. This selective binding of olmesartan to the AT 1 -R is coupled with a high degree of insurmountability and demonstrated a greater binding affinity than most of the other commercially available ARBs.…”

Obtención y estudio de complejos de coordinación con biometales y ligandos con actividad biológica

“…Además, su excelente tolerancia general se refleja en efectos secundarios leves y transitorios, que tienden a desaparecer con el tiempo. Su perfil de seguridad es particularmente notable en comparación con otros fármacos para la hipertensión 210,211 . El olmesartán se suministra como olmesartán medoxomilo (Figura I-10), que es la pro-droga que hidroliza in vivo a la forma activa olmesartán 212 .…”