Pharmacokinetic evaluation and clinical utility of azilsartan medoxomil for the treatment of hypertension

Angeli, Fabio; Verdecchia, Paolo; Pascucci, Chiara; Poltronieri, Cristina; Reboldi, Gianpaolo

doi:10.1517/17425255.2013.769521

Cited by 22 publications

(15 citation statements)

References 42 publications

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“…In our preliminary study, we observed that AZL-M concentration rose sharply 0.5 hours after administration and disappeared after 24 hours in both the normal and CSQ-tg mice (data not shown), in contrast to long-lasting pharmacokinetics in humans (Angeli et al, 2013). Also, 3-day-administration in CSQ-tg mice might be too short to achieve steady anti-hypertensive effect.…”

Section: Discussionmentioning

confidence: 84%

AT1 receptor blocker azilsartan medoxomil normalizes plasma miR-146a and miR-342-3p in a murine heart failure model

et al. 2016

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Our study measured circulating microRNA (miRNA) levels in the plasma of calsequestrin (CSQ)-tg mouse, a severe heart failure model, and evaluated whether treatment with angiotensin II type 1 receptor blocker, azilsartan medoxomil (AZL-M) influenced their levels using miRNA array analysis. MiR-146a, miR-149, miR-150, and miR-342-3p were reproducibly reduced in the plasma of CSQ-tg mice. Among them, miR-146a and miR-342-3p were significantly restored by AZL-M, which were associated with improvement of survival rate and reduction of congestion. These results suggest that miRNA, especially miR-146a and miR-342-3p, could be used as potential biomarkers for evaluating the efficacy of anti-heart failure drugs.

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Section: Discussionmentioning

confidence: 84%

AT1 receptor blocker azilsartan medoxomil normalizes plasma miR-146a and miR-342-3p in a murine heart failure model

et al. 2016

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“…Beside antihypertensive drugs such as thiazide diuretics, β‐adrenoceptor antagonists (BAA) and calcium channel blockers, which have an effect on blood volume, heart rate and vasodilation, respectively , an important therapeutic approach for hypertension is the blockade of the renin–angiotensin–aldosterone system (RAAS). Azilsartan (AZL) was recently introduced for treatment of hypertension mainly due to unprecedented tight binding to the angiotensin receptor, AT 1 , and the pharmacokinetic and testing in animal studies as well as a proposed role in the human clinic have recently been reviewed . Here, we have focused on the strong interaction of the drug with the AT 1 receptor and whether that is reflected in the clinical effects of the drug and compared with other angiotensin receptor antagonists.…”

mentioning

confidence: 99%

Azilsartan Medoxomil, an Angiotensin II Receptor Antagonist for the Treatment of Hypertension

Hjermitslev

Grimm

Wehland

et al. 2017

Basic Clin Pharma Tox

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Azilsartan (AZL) medoxomil was approved by the United States Food and Drug Administration in 2011 for the treatment of hypertension and has shown promising results both in blood pressure (BP) reduction and in tolerability, but has not yet been taken into practice to the same extent as other angiotensin II receptor blockers (ARBs) that have been on the market for a longer period. AZL antagonizes the AT 1 receptor for angiotensin II (ANG II), whereas angiotensin-converting enzyme inhibitors block the conversion of angiotensin I to ANG II, but not alternative routes of formation of ANG II. The bioavailability of AZL is about 60% and it has a t max of 1.5-3 hr and a half-life of approximately 11 hr. With its IC 50 of 7.4 nM after 5 hr of drug washout in radioligand assays, AZL has a tighter and longer-lasting binding to the AT 1 receptor by several orders of magnitude than other ARBs, which might lead to a more effective reduction in BP. Clinical studies have revealed that AZL doses of 40 and 80 mg/day reduce BP significantly better than maximal clinical doses of valsartan or olmesartan, while being well tolerated and exhibiting a spectrum of adverse effects comparable to those of other ARBs. These properties of AZL might lower the risk of cardiovascular disease and thereby reduce mortality rates. However, the existing mortality studies have not found this correlation, which should be further investigated.

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“…Angiotensin II receptor blockers (ARBs) are a drug class generally considered to be among the best tolerated and more effective agents in the realm of antihypertensives, even though there are some differences between individual drugs . The eighth and the most recently approved drug of the ARBs is azilsartan medoxomil (AZL‐M); it is approved at doses of 20 to 80 mg once daily (40 to 80 mg in the United States), alone or in combination with other antihypertensive agents …”

mentioning

confidence: 99%

“…[5][6][7][8][9][10] The eighth and the most recently approved drug of the ARBs is azilsartan medoxomil (AZL-M); it is approved at doses of 20 to 80 mg once daily (40 to 80 mg in the United States), alone or in combination with other antihypertensive agents. [11][12][13][14][15][16][17] AZL-M is a prodrug potassium salt that is rapidly hydrolyzed to the active moiety, AZL, and is not detected in plasma after oral administration. After oral administration of AZL-M, peak plasma concentrations of AZL are reached within 1.5 to 3 hours.…”

mentioning

confidence: 99%

Single‐Center Evaluation of the Pharmacokinetics and Safety of the Angiotensin II Receptor Antagonist Azilsartan Medoxomil in Mild to Moderate Hepatic Impairment

Dudkowski

Karim

Zhao

et al. 2017

The Journal of Clinical Pharma

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Azilsartan medoxomil (AZL‐M) is a potent angiotensin II receptor blocker that decreases blood pressure in a dose‐dependent manner. It is a prodrug that is not detected in blood after its oral administration because of its rapid hydrolysis to the active moiety, azilsartan (AZL). AZL undergoes further metabolism to the major metabolite, M‐II, and minor metabolites. The objective of this study was to determine the effect of mild to moderate hepatic impairment on the pharmacokinetics of AZL and its major metabolite. This was a single‐center, open‐label, phase 1 parallel‐group study that examined the single‐dose (day 1) and multiple‐dose (days 4–8) — 40 mg — pharmacokinetics of AZL and M‐II in 16 subjects with mild and moderate hepatic impairment by Child‐Pugh classification (n = 8 per group) and subjects (n = 16) matched based on age, sex, race, weight, and smoking status. Mild or moderate hepatic impairment did not cause clinically meaningful increases in exposure to AZL and M‐II. Mild or moderate hepatic impairment had no clinically meaningful effect on the plasma protein binding of AZL and M‐II. Single and multiple doses of AZL‐M 40 mg were well tolerated in all subject groups. Based on the pharmacokinetic and tolerability findings, no dose adjustment of AZL‐M is required for subjects with mild and moderate hepatic impairment.

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Pharmacokinetic evaluation and clinical utility of azilsartan medoxomil for the treatment of hypertension

Cited by 22 publications

References 42 publications

AT1 receptor blocker azilsartan medoxomil normalizes plasma miR-146a and miR-342-3p in a murine heart failure model

AT1 receptor blocker azilsartan medoxomil normalizes plasma miR-146a and miR-342-3p in a murine heart failure model

Azilsartan Medoxomil, an Angiotensin II Receptor Antagonist for the Treatment of Hypertension

Single‐Center Evaluation of the Pharmacokinetics and Safety of the Angiotensin II Receptor Antagonist Azilsartan Medoxomil in Mild to Moderate Hepatic Impairment

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