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| __NOTOC__
| | #REDIRECT [[Azilsartan kamedoxomil#Pharmacology]] |
| {{Azilsartan}}
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| {{CMG}}; {{AE}} {{SS}}
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| ==Clinical Pharmacology==
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| ===Pharmacodynamics===
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| Azilsartan inhibits the pressor effects of an angiotensin II infusion in a dose-related manner. An azilsartan single dose equivalent to 32 mg azilsartan medoxomil inhibited the maximal pressor effect by approximately 90% at peak, and approximately 60% at 24 hours. Plasma angiotensin I and II concentrations and plasma renin activity increased while plasma aldosterone concentrations decreased after single and repeated administration of Edarbi to healthy subjects; no clinically significant effects on serum potassium or sodium were observed.
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| Effect on Cardiac Repolarization
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| A thorough QT/QTc study was conducted to assess the potential of azilsartan to prolong the QT/QTc interval in healthy subjects. There was no evidence of QT/QTc prolongation at a dose of 320 mg of Edarbi.
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| ===Pharmacokinetics===
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| ====Absorption====
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| Azilsartan medoxomil is hydrolyzed to azilsartan, the active metabolite, in the gastrointestinal tract during absorption. Azilsartan medoxomil is not detected in plasma after oral administration. Dose proportionality in exposure was established for azilsartan in the azilsartan medoxomil dose range of 20 mg to 320 mg after single or multiple dosing.
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| The estimated absolute bioavailability of azilsartan following administration of azilsartan medoxomil is approximately 60%. After oral administration of azilsartan medoxomil, peak plasma concentrations (Cmax) of azilsartan are reached within 1.5 to 3 hours. Food does not affect the bioavailability of azilsartan.
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| ====Distribution====
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| The volume of distribution of azilsartan is approximately 16 L. Azilsartan is highly bound to human plasma proteins (>99%), mainly serum albumin. Protein binding is constant at azilsartan plasma concentrations well above the range achieved with recommended doses.
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| In rats, minimal azilsartan-associated radioactivity crossed the blood-brain barrier. Azilsartan passed across the placental barrier in pregnant rats and was distributed to the fetus.
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| ====Metabolism and Elimination====
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| Azilsartan is metabolized to two primary metabolites. The major metabolite in plasma is formed by O-dealkylation, referred to as metabolite M-II, and the minor metabolite is formed by decarboxylation, referred to as metabolite M-I. Systemic exposures to the major and minor metabolites in humans were approximately 50% and less than 1% of azilsartan, respectively. M-I and M-II do not contribute to the pharmacologic activity of Edarbi. The major enzyme responsible for azilsartan metabolism is CYP2C9.
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| Following an oral dose of 14C-labeled azilsartan medoxomil, approximately 55% of radioactivity was recovered in feces and approximately 42% in urine, with 15% of the dose excreted in urine as azilsartan. The elimination half-life of azilsartan is approximately 11 hours and renal clearance is approximately 2.3 mL/min. Steady-state levels of azilsartan are achieved within five days, and no accumulation in plasma occurs with repeated once-daily dosing.
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| ====Special Populations====
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| The effect of demographic and functional factors on the pharmacokinetics of azilsartan was studied in single and multiple dose studies. Pharmacokinetic measures indicating the magnitude of the effect on azilsartan are presented in Figure 1 as change relative to reference (test/reference). Effects are modest and do not call for dosage adjustment.
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| Figure 1. Impact of intrinsic factors on the pharmacokinetics of azilsartan
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| {|
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| |[[File:Azilsartan04.jpg|thumb|800px]]
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| |}<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = EDARBI (AZILSARTAN KAMEDOXOMIL) TABLET [TAKEDA PHARMACEUTICALS AMERICA, INC.] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=75b16bfc-38c1-4133-bd7d-13258d54edec | publisher = | date = | accessdate = 19 February 2014 }}</ref>
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| ==References==
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| {{Reflist}}
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| [[Category:Angiotensin II receptor antagonists]]
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| [[Category:Benzimidazoles]]
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| [[Category:Carbamates]]
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| [[Category:Ethers]]
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| [[Category:Cardiovascular Drugs]]
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| [[Category:Drugs]]
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