Olmesartan medoxomil: influence of age, renal and hepatic function on the pharmacokinetics of olmesartan medoxomil

Bergmann, Klaus von; Laeis, Petra; Püchler, Kurt; Sudhop, Thomas; Schwocho, Lee; Gonzalez, Lisette

doi:10.1097/00004872-200106001-00005

Cited by 59 publications

(64 citation statements)

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“…4 As shown in Table 2, C max and AUC at steady state were greater than controls for all patient groups except for those with mild hepatic impairment. In patients with severe renal impairment, in whom exposure is increased 2.79-fold compared with healthy subjects, caution is required when starting therapy, and the daily dose of olmesartan medoxomil should not exceed 20 mg.…”

Section: Effect Of Potential Risk-group Status On Pharmacokineticsmentioning

confidence: 79%

“…However, only a fraction (26%) of the administered dose is available systemically and, of this, up to half is excreted in the urine and the remainder in the faeces with unabsorbed drug. 3,4 …”

Section: Pharmacokinetic Parametersmentioning

confidence: 99%

“…4 The parameters in elderly, very elderly, renally impaired and hepatically impaired patients were compared with appropriate controls as follows:…”

Section: Effect Of Potential Risk-group Status On Pharmacokineticsmentioning

confidence: 99%

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The new oral angiotensin II antagonist olmesartan medoxomil: a concise overview

Brunner

2002

J Hum Hypertens

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The new orally active angiotensin II (A II) type-1 receptor antagonist olmesartan medoxomil is a prodrug, which is rapidly converted in vivo to the active metabolite, olmesartan. The pharmacology, antihypertensive efficacy and safety of olmesartan medoxomil and/or the pharmacologically active metabolite, olmesartan, have been evaluated in both non-clinical and clinical models. Orally administered olmesartan medoxomil is rapidly absorbed from the gastrointestinal tract and converted during absorption to olmesartan, which is subsequently excreted without further metabolism. Peak plasma concentrations of olmesartan occur 1-3 h after administration, after which concentrations decrease with an elimination half-life of 10-15 h. The absolute bioavailability of olmesartan from olmesartan medoxomil tablets is 28.6%. In a single-dose crossover study in 16 patients with mild-to-moderate hypertension receiving a sodium-restricted diet, statistically significant lowering

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Section: Effect Of Potential Risk-group Status On Pharmacokineticsmentioning

confidence: 79%

Section: Pharmacokinetic Parametersmentioning

confidence: 99%

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The new oral angiotensin II antagonist olmesartan medoxomil: a concise overview

Brunner

2002

J Hum Hypertens

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“…17 However, the C max and AUC were 44% higher and the elimination halflife longer (16.5 vs 12.3 h) in the older (475 years) vs the younger (446 years of age) subjects. 17,19 In addition the C max was affected by renal and liver function, being higher (82 vs 39%) in patients with renal failure vs controls and (48 vs 30%) in patients with moderately severe vs mild liver failure. 19 Olmesartan medoxomil has a 26% bioavailability after oral administration and is mainly eliminated through the gastrointestinal tract and the kidney (50-65 and 10-16%) respectively.…”

Section: Pharmacokinetic and Pharmacodynamic Profilementioning

confidence: 99%

“…17,19 In addition the C max was affected by renal and liver function, being higher (82 vs 39%) in patients with renal failure vs controls and (48 vs 30%) in patients with moderately severe vs mild liver failure. 19 Olmesartan medoxomil has a 26% bioavailability after oral administration and is mainly eliminated through the gastrointestinal tract and the kidney (50-65 and 10-16%) respectively. 17,20 The terminal half-life of olmesartan is approximately 13 h, which makes it suitable for once daily administration.…”

Section: Pharmacokinetic and Pharmacodynamic Profilementioning

confidence: 99%

Treatment of hypertension with olmesartan medoxomil, alone and in combination with a diuretic: an update

2007

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Olmesartan medoxomil is an angiotensin II (Ang II) receptor blocker (ARB) that has been approved by the US Food and Drug Administration (FDA) for the treatment of hypertension. It is a prodrug that is hydrolysed in the gut into its active metabolite, olmesartan (RNH-6270). Olmesartan is highly selective for the Ang II type 1 receptor (AT1) to which it binds completely and insurmountably and has very little affinity for the other receptor subtypes AT2 and AT4. After oral administration, in animals and humans, it achieves a maximal blood drug concentration within a maximal time of approximately 2 h. It is then slowly eliminated in the urine and faeces. His half-life is approximately 13 h, which makes it suitable for once-daily administration. Olmesartan medoxomil given orally in single daily doses of 20-40 mg has demonstrated significant blood pressure (BP) lowering effects in hypertensive patients. A medline search for the preparation of this manuscript was conducted and revealed 128 references, from 2000 to 2007. Of these, only 16 well-designed prospective clinical trials were selected. The remaining were either animal studies, reviews or studies in progress. In well-designed clinical trials, olmesartan medoxomil has demonstrated similar antihypertensive actions to the other antihypertensive drugs, as well as other members of its class given the highest recommended doses. In addition, the BP lowering effect of olmesartan, like the other members of its class, is greatly enhanced in combination with a diuretic. Its safety profile is similar to the other ARBs and no different than placebo.

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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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Olmesartan medoxomil: influence of age, renal and hepatic function on the pharmacokinetics of olmesartan medoxomil

Cited by 59 publications

References 0 publications

The new oral angiotensin II antagonist olmesartan medoxomil: a concise overview

The new oral angiotensin II antagonist olmesartan medoxomil: a concise overview

Treatment of hypertension with olmesartan medoxomil, alone and in combination with a diuretic: an update

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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