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| __NOTOC__
| | #REDIRECT [[Olmesartan#Pharmacology]] |
| {{Olmesartan}}
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| {{CMG}}; {{AE}} {{SS}}
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| ==Clinical Pharmacology==
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| ===Pharmacodynamics===
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| Benicar doses of 2.5 mg to 40 mg inhibit the pressor effects of [[angiotensin ]]I infusion. The duration of the inhibitory effect was related to dose, with doses of Benicar >40 mg giving >90% inhibition at 24 hours.
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| Plasma concentrations of [[angiotensin ]]I and [[angiotensin ]]II and plasma renin activity (PRA) increase after single and repeated administration of Benicar to healthy subjects and hypertensive patients. Repeated administration of up to 80 mg Benicar had minimal influence on aldosterone levels and no effect on serum potassium.
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| ===Pharmacokinetics===
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| ====Absorption ====
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| Olmesartan medoxomil is rapidly and completely bioactivated by ester hydrolysis to olmesartan during absorption from the gastrointestinal tract. | |
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| Benicar tablets and the suspension formulation prepared from Benicar tablets are bioequivalent [see Dosage and Administration (2.2)].
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| The absolute bioavailability of olmesartan is approximately 26%. After oral administration, the peak plasma concentration (Cmax) of olmesartan is reached after 1 to 2 hours. Food does not affect the bioavailability of olmesartan.
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| ====Distribution ====
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| The volume of distribution of olmesartan is approximately 17 L. Olmesartan is highly bound to plasma proteins (99%) and does not penetrate red blood cells. The protein binding is constant at plasma olmesartan concentrations well above the range achieved with recommended doses.
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| In rats, olmesartan crossed the blood-brain barrier poorly, if at all. Olmesartan passed across the placental barrier in rats and was distributed to the fetus. Olmesartan was distributed to milk at low levels in rats.
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| ====Metabolism and Excretion====
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| Following the rapid and complete conversion of olmesartan medoxomil to olmesartan during absorption, there is virtually no further metabolism of olmesartan. Total plasma clearance of olmesartan is 1.3 L/h, with a renal clearance of 0.6 L/h. Approximately 35% to 50% of the absorbed dose is recovered in urine while the remainder is eliminated in feces via the bile.
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| Olmesartan appears to be eliminated in a biphasic manner with a terminal elimination half-life of approximately 13 hours. Olmesartan shows linear pharmacokinetics following single oral doses of up to 320 mg and multiple oral doses of up to 80 mg. Steady-state levels of olmesartan are achieved within 3 to 5 days and no accumulation in plasma occurs with once-daily dosing.
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| ====Geriatric ====
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| The pharmacokinetics of olmesartan were studied in the elderly (≥65 years). Overall, maximum plasma concentrations of olmesartan were similar in young adults and the elderly. Modest accumulation of olmesartan was observed in the elderly with repeated dosing; AUCss, τ was 33% higher in elderly patients, corresponding to an approximate 30% reduction in CLR [see Dosage and Administration (2.1) and Use in Specific Populations (8.5)].
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| ====Pediatric ====
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| The pharmacokinetics of olmesartan were studied in pediatric hypertensive patients aged 1 to16 years. The clearance of olmesartan in pediatric patients was similar to that in adult patients when adjusted by the body weight [see Use in Specific Populations (8.4)].
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| Olmesartan pharmacokinetics have not been investigated in pediatric patients less than 1 year of age [see Warnings and Precautions (5.2) and Use in Specific Populations (8.4)].
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| ====Gender====
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| Minor differences were observed in the pharmacokinetics of olmesartan in women compared to men. AUC and Cmax were 10-15% higher in women than in men.
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| ====Hepatic Insufficiency====
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| Increases in AUC0-∞ and Cmax were observed in patients with moderate hepatic impairment compared to those in matched controls, with an increase in AUC of about 60%[see Dosage and Administration (2.1) and Use in Specific Populations (8.6)].
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| ====Renal Insufficiency====
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| In patients with renal insufficiency, serum concentrations of olmesartan were elevated compared to subjects with normal renal function. After repeated dosing, the AUC was approximately tripled in patients with severe renal impairment (creatinine clearance <20 mL/min). The pharmacokinetics of olmesartan in patients undergoing [[hemodialysis ]]has not been studied [see Dosage and Administration (2.1), Warnings and Precautions (5.4) and Use in Specific Populations (8.7)].
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| ===Drug Interactions===
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| ====Bile acid sequestering agent colesevelam====
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| Concomitant administration of 40 mg olmesartan medoxomil and 3750 mg colesevelam [[hydrochloride]]in healthy subjects resulted in 28% reduction in Cmax and 39% reduction in AUC of olmesartan. Lesser effects, 4% and 15% reduction in Cmax and AUC respectively, were observed when olmesartan m edoxomil was administered 4 hours prior to colesevelam [[hydrochloride]][see Drug Interactions (7)].<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = BENICAR (OLMESARTAN MEDOXOMIL) TABLET, FILM COATED [DAIICHI SANKYO, INC] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=33770d80-754f-11de-8dba-0002a5d5c51b | publisher = | date = | accessdate = 21 February 2014 }}</ref>
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| ==References==
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| {{Reflist}}
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| {{[[angiotensin ]]II receptor antagonists}}
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| [[Category:[[angiotensin ]]II receptor antagonists]]
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| [[Category:Imidazoles]]
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| [[Category:Tetrazoles]]
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| [[Category:Carboxylate esters]]
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| [[Category:Alcohols]]
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| [[Category:Biphenyls]]
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| [[Category:Cardiovascular Drugs]]
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| [[Category:Drugs]]
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