The pharmacokinetic and metabolic profile of olmesartan medoxomil limits the risk of clinically relevant drug interaction

Laeis, Petra; Püchler, Kurt; Kirch, Wilhelm

doi:10.1097/00004872-200106001-00004

Cited by 126 publications

(98 citation statements)

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“…It has been reported that olmesartan has a dual clearance pathway, with B60% of a dose being excreted into feces via bile and the remaining 40% being excreted into the urine, 1,2 and that multiple transporters in multiple tissues were involved in the overall pharmacokinetics of olmesartan. 3 Therefore, the effect of genetic variations of single transporters on the pharmacokinetics of olmesartan is considered to be small.…”

Section: Discussionmentioning

confidence: 99%

“…Olmesartan is excreted into both bile and urine without undergoing metabolism. 1 Some studies have suggested that organic anion-transporting polypeptide 1B1 (gene name, SLCO1B1) and organic anion-transporting polypeptide 1B3 (SLCO1B3) are involved in hepatic uptake and that the ATP-binding cassette, sub-family C member 2 (multidrug resistance-associated protein (MRP) 2, ABCC2), is involved in the biliary excretion of olmesartan. 2,3 Membrane transporters have important roles in the uptake, distribution and excretion of endogenous compounds and xenobiotics.…”

Section: Introductionmentioning

confidence: 99%

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Association study of genetic polymorphisms of drug transporters, SLCO1B1, SLCO1B3 and ABCC2, in African-Americans, Hispanics and Caucasians and olmesartan exposure

et al. 2012

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It has been reported that organic anion-transporting polypeptide (OATP) 1B1, OATP1B3 and multidrug resistance-associated protein 2 are involved in the hepatobiliary transport of olmesartan. We investigated the association of SLCO1B1, SLCO1B3 and ABCC2 polymorphisms with the pharmacokinetics of olmesartan. We sequenced all exons, exon-intron junctions and the 5 0 and 3 0 flanking regions of the three genes in 115 individuals from African-American, Hispanic and Caucasian populations who had participated in our clinical studies. A total of 348 single-nucleotide polymorphisms (SNPs) were identified with a minor allele frequency of X0.01 in at least one population; 132 SNPs were detected in SLCO1B1, 130 in SLCO1B3 and 86 in ABCC2. We characterized the linkage disequilibrium (LD) and haplotypes shared across the populations and then evaluated the association between the haplotypes and the pharmacokinetics of olmesartan. Seven inter-ethnic LD blocks were observed in SLCO1B1, while three in SLCO1B3 and four in ABCC2. Although extensive variability in the sequences of SLCO1B1, SLCO1B3 and ABCC2 existed across the three populations, there was no remarkable difference in any pharmacokinetic parameters of olmesartan between subjects with and without any major haplotypes in the three transporter genes we tested.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association study of genetic polymorphisms of drug transporters, SLCO1B1, SLCO1B3 and ABCC2, in African-Americans, Hispanics and Caucasians and olmesartan exposure

et al. 2012

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“…The medoxomil ester of olmesartan was developed in preference to the active compound olmesartan, because the oral bioavailability of the latter is low (4.5%) and is increased (to 28.6%) 3 by esterification with the medoxomil moiety. Following oral administration of olmesartan medoxomil in humans and animals, the intact parent ester has not been observed in measurable amounts in plasma or excreta.…”

Section: Pharmacokinetic Parametersmentioning

confidence: 99%

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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“…Peak plasma concentrations of OLM occurred 1-3 h after administration, after which concentrations decreased quickly. The elimination half-life was 10-15 h. Bioavailability increased proportionally with dose, after single and multiple daily oral doses, over the therapeutic dose range, up to 40-80 mg daily [6].…”

Section: Introductionmentioning

confidence: 96%

Method Development and Validation of Liquid Chromatography-Tandem Mass Spectrometry for Angiotensin-II in Human Plasma: Application to Study Interaction Between Atorvastatin & Olmesartan Drug Combination

Pal

2014

Ind J Clin Biochem

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Simple and sensitive Liquid ChromatographyTandem Mass Spectrometry (LCMS/MS) method was developed and validated, then was implicated on hypertensive human subjects to study drug interaction of atorvastatin (ATVS) and Olmesartan (OLM) on status of Angiotensin-II (ANG-II). The ANG-II in plasma was extracted with 5 mL methanol containing 5 % formic acid through C 18 (cartridges) liquid-liquid extraction, dried and reconstituted with 1 mL of 16 % acetonitrile in 0.1 % formic acid in water. The chromatographic separation of ANG-II with a Agilent technology 6410 Triple quadrupole was carried multiple reaction monitoring scan mode with a Agilent 1290 Infinity LC system for UHPLC. The sample were separated on a (Thermo Scientific) Hy-Purity advance (50 9 4.6 mm, 5 lm) using Mobile Phase A: 16 % acetonitrile in 0.1 % formic acid in water and Mobile Phase B: 0.1 % formic acid in methanol at a flow rate of 0.3 mL/min, performed at ambient temperature. The mobile phase gradient of 16 % acetonitrile in water was linearly increased to 38 % acetonitrile over 10 min and subsequently the mobile-phase was increased to 100 % acetonitrile over 15 min. The developed method was validated for specificity, accuracy, precision, stability, linearity, sensitivity and recovery. The method was linear between peak area ratio of standard and internal standard over the range of 50-800 ng/mL. The method was successfully applied for the drug interaction study revealed levels of ANG-II were significantly higher in ATV-S ? OLM treatment condition as compared to individual treatment of OLM. This reflects the reason of low effectiveness of ATVS ? OLM in combination instead of synergistic activity.

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The pharmacokinetic and metabolic profile of olmesartan medoxomil limits the risk of clinically relevant drug interaction

Cited by 126 publications

References 0 publications

Association study of genetic polymorphisms of drug transporters, SLCO1B1, SLCO1B3 and ABCC2, in African-Americans, Hispanics and Caucasians and olmesartan exposure

Association study of genetic polymorphisms of drug transporters, SLCO1B1, SLCO1B3 and ABCC2, in African-Americans, Hispanics and Caucasians and olmesartan exposure

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

Method Development and Validation of Liquid Chromatography-Tandem Mass Spectrometry for Angiotensin-II in Human Plasma: Application to Study Interaction Between Atorvastatin & Olmesartan Drug Combination

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