Olmesartan medoxomil: pharmacological properties, therapeutic efficacy and tolerability

General Description

Olmesartan medoxomil is an angiotensin II receptor blocker (ARB) that effectively blocks the actions of angiotensin II. It has shown potential in counteracting vasoconstriction and pressor responses caused by angiotensin II. Olmesartan medoxomil increases plasma renin, reduces aldosterone excretion, and improves arterial compliance. It lowers diastolic blood pressure and has shown protective effects against end-organ damage. After oral administration, it is rapidly absorbed and converted to the active metabolite. Olmesartan medoxomil has high plasma protein binding, low volume of distribution, and is eliminated primarily through feces. Clinical trials have shown that olmesartan medoxomil is an effective antihypertensive medication, reducing blood pressure in patients with hypertension. It is well-tolerated, with mild and transient adverse events. Overall, olmesartan medoxomil is a safe and efficacious treatment option for hypertension.

Figure 1. Tablets of olmesartan medoxomil

Pharmacological properties

Olmesartan medoxomil is an angiotensin II receptor blocker (ARB) that selectively binds to the AT1 receptor, effectively blocking the actions of angiotensin II. It has a high affinity for the receptor and shows insurmountable binding. Animal studies have demonstrated its ability to counteract vasoconstriction and pressor responses caused by angiotensin II. In healthy volunteers, Olmesartan medoxomil increases plasma renin, reduces aldosterone excretion, and improves arterial compliance. In hypertensive patients, it lowers diastolic blood pressure while increasing plasma renin activity and angiotensin II levels. There is also preliminary evidence suggesting its protective effects against end-organ damage, particularly in terms of renal protection and anti-atherosclerotic activity. After oral administration, olmesartan medoxomil, the prodrug form, is rapidly absorbed and converted to the active metabolite, olmesartan, in the gastrointestinal tract. The bioavailability is 26% following a 20 mg dose in healthy individuals, with peak plasma levels achieved after approximately 2 hours. Olmesartan medoxomil has high plasma protein binding and a low volume of distribution. It is eliminated primarily through feces via the hepato-biliary route, with minimal urinary excretion. The long elimination half-life allows for once-daily dosing. Olmesartan medoxomil rarely requires dosage adjustment and exhibits a low potential for pharmacokinetic drug interactions. ¹

Therapeutic efficacy

Extensive clinical trials have shown that oral olmesartan medoxomil is an effective antihypertensive medication. It has been tested in large-scale, double-blind studies involving over 150 patients, and its efficacy has been confirmed in reducing blood pressure (BP) in adult patients with hypertension, including those with mild to moderate hypertension. The trials also demonstrated that olmesartan medoxomil was more effective than placebo in lowering BP, with the effects sustained throughout the dosage interval. In comparison to other antihypertensive medications, olmesartan medoxomil monotherapy was found to be equally effective as amlodipine and felodipine, and more effective than atenolol and captopril in reducing DBP. Combination therapy with olmesartan medoxomil and hydrochlorothiazide (HCTZ) was also shown to significantly reduce both DBP and SBP compared to placebo or individual components alone. Although noninferiority between olmesartan medoxomil monotherapy and combination therapy with HCTZ was not established in one trial, this was attributed to a high response rate during monotherapy resulting in fewer patients entering the double-blind phase. However, in another trial, combination therapy with olmesartan medoxomil and HCTZ demonstrated superior efficacy compared to losartan plus HCTZ or atenolol plus HCTZ in reducing DBP and SBP. Overall, olmesartan medoxomil has proven to be an effective and well-tolerated treatment option for hypertension, either as monotherapy or in combination with HCTZ. It consistently lowers BP, demonstrates a faster onset of action, and provides comparable or better results compared to other ARBs and antihypertensive medications. ²

Tolerability

In clinical trials lasting up to 24 weeks, oral olmesartan medoxomil, either as monotherapy or in combination with HCTZ, was well tolerated by patients with hypertension or isolated systolic hypertension (ISH). The incidence of treatment-emergent adverse events was similar to that of placebo, and the events were generally mild, transient, and did not show a dose-response relationship. Only a small percentage of patients (≤2.4%) discontinued treatment due to adverse events. The most common adverse event reported with olmesartan medoxomil monotherapy was dizziness, occurring in 2.8% of patients compared to 0.9% in the placebo group. When combined with HCTZ, additional adverse events with an incidence of ≥2% and numerically higher than placebo included dizziness, upper respiratory tract infection, hyperuricemia, and nausea (all ≤9% with olmesartan medoxomil plus HCTZ). There were no significant differences in the nature or incidence of adverse events between olmesartan medoxomil and other active comparator groups. Overall, these findings indicate that olmesartan medoxomil is well tolerated and has a favorable safety profile for the treatment of hypertension. ³

Reference

1. Mire DE, Silfani TN, Pugsley MK. A review of the structural and functional features of olmesartan medoxomil, an angiotensin receptor blocker. J Cardiovasc Pharmacol, 2005; 46(5): 585–593.

2. Martínez-Martín FJ, Macías-Batista A, Rodríguez-Rosas H, et al. Effects of olmesartan on insulin sensitivity in non-diabetic hypertensive patients with metabolic syndrome. J Hypertens, 2005; 23: 103.

3. Scott LJ, McCormack PL. Olmesartan medoxomil: a review of its use in the management of hypertension. Drugs. 2008; 68(9): 1239-1272.

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