Olmesartan medoxomyl is a white to light yellowish-white crystalline powder, almost insoluble in water and difficult to dissolve in methanol. Molecular weight is 558.59.
Pharmacological action - antihypertensive.
Olmesartan selectively blocks angiotensin II receptors (AT1 subtype). Suppresses AT1-mediated receptor effects of angiotensin II (including such effects as vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, increased renal sodium reabsorption). Does not affect kinase II (ACE), which destroys bradykinin and participates in the formation of angiotensin II.
At arterial hypertension olmesartan causes dose-dependent long term decrease of AP. Taking medoxomil olmesartan once a day provides an effective and mild decrease in APF for 24 hours. The hypotensive effect of olmesartan develops usually within 1-2 weeks, and the maximum effect is approximately 8 weeks after the start of therapy.
Olmesartana medoxomil is a prodrug. In the process of absorption from the gastrointestinal tract undergoes hydrolysis and quickly and completely turns into a pharmacologically active form - olmesartan. Absolute bioavailability of olmesartan is about 26%, food intake has no significant impact on bioavailability. After oral intake of Cmax olmesartan in plasma is achieved within 1-2 hours. Binding of olmesartan to plasma proteins is 99%, binding to blood cells is insignificant. The volume of distribution of olmesartan is about 17.1 l. Css is achieved within 3-5 days. Total plasma clearance of olmesartan is 1.3 l/h, renal clearance is 0.6 l/h. It is excreted by kidneys (approximately 40 %) and bile (approximately 60 %). The elimination of olmesartan is biphasic, terminal T1/2 is about 13 hours.
Pharmacokinetics in special clinical cases
Age. Olmesartan Dosage Cmax values were similar for young people and for people over 65 years of age. Older people showed moderate olmesartan accumulation at repeated doses, a 33% increase in AUC and a 30% decrease in renal clearance.
Paul. Insignificant differences in pharmacokinetic parameters of olmesartan were observed by sex: AUC and Cmax were 10-15% higher in women than in men.
Abnormal renal function. In patients with severe renal failure (Cl creatinine <20 ml/min) AUC in equilibrium was increased by 3 times.
Disturbance of liver function. Increases in AUC (about 60%) and Cmax were observed in patients with moderate liver dysfunction compared to these parameters in healthy volunteers.
Application of Olmesartan medoxomyl substance
Essential arterial hypertension.
Hypersensitivity, biliary obstruction, renal failure (Cl creatinine <20 ml/min), condition after kidney transplantation (no clinical experience), pregnancy, breastfeeding.
Restrictions on use
Stenosis of aortic or mitral valves, hypertrophic obstructive cardiomyopathy, primary hyperaldosteronism, hyperkalemia, hyponatremia (risk of dehydration, arterial hypotension, renal failure), renal failure (Cl creatinine >20 ml/min), Chronic heart failure, bilateral renal artery stenosis or single kidney artery stenosis, CHD, cerebrovascular disease, age over 65, liver function disorders, conditions accompanied by a decrease in OCC (i.e.(including diarrhoea, vomiting), as well as when following a diet with restriction of sodium; simultaneous use with diuretics, age under 18 years (efficacy and safety of use have not been determined).