Pharmacokinetics of Amlodipine and Olmesartan After Administration of Amlodipine Besylate and Olmesartan Medoxomil in Separate Dosage Forms and as a Fixed‐Dose Combination

Rohatagi, Shashank; Lee, James; Shenouda, Magdy; Haworth, Stephen J.; Bathala, Mohinder S.; Allison, Mark; Rubets, Igor; Heyrman, Reinilde; Noveck, Robert J.; Salazar, Daniel E.

doi:10.1177/0091270008322176

Cited by 28 publications

(23 citation statements)

References 17 publications

(43 reference statements)

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“…No significant pharmacokinetic drug–drug interactions occur when olmesartan medoxomil and amlodipine are co-administered in separate dosage forms 28,29. When orally administered as a fixed-dose combination, amlodipine/olmesartan medoxomil is bioequivalent to single-entity dosage forms of both drugs 28…”

Section: Amlodipine/olmesartan Medoxomil: Pharmacokinetics and Mechanmentioning

confidence: 99%

“…28 For example, following a single dose of the combination tablet, peak plasma concentrations of amlodipine and olmesartan were 7.6 and 833.3 ng/mL, and values for the area under the plasma concentration-time curve were 424.8 and 5,374.2 ng·h/mL, respectively 28. Corresponding values following administration of amlodipine 10 mg and olmesartan medoxomil 40 mg as two separate dosage forms were 7.4 and 810.3 ng/mL and 410.9 and 5,418.6 ng·h/mL, respectively 28…”

Section: Amlodipine/olmesartan Medoxomil: Pharmacokinetics and Mechanmentioning

confidence: 99%

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Critical appraisal of amlodipine and olmesartan medoxomil fixed-dose combination in achieving blood pressure goals

Basile

2010

IBPC

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Hypertension remains a significant health burden in the United States, with almost one in three adults affected, and is an independent risk factor for cardiovascular and renal disease. The goal of antihypertensive treatment is to reduce cardiovascular and renal morbidity and mortality by reducing blood pressure (BP). Guidelines recommend a target BP of <140/90 mmHg, with a more stringent goal of <130/80 mmHg for patients with diabetes and chronic renal disease. However, BP goal attainment rates remain low and most patients require therapy with two or more antihypertensive agents. Combination antihypertensive therapy usually employs agents from different classes, thus benefitting from complementary mechanisms of action to achieve greater BP control with fewer side effects. Patient adherence to therapy is enhanced by formulating treatments as fixed-dose (single-pill) combinations. One example is the combination of amlodipine, a dihydropyridine calcium channel blocker (CCB), with olmesartan medoxomil, an angiotensin receptor blocker (ARB). Here, the rationale for the use of CCB/ARB combination therapy is discussed, as well as the pharmacology and tolerability of the amlodipine/olmesartan medoxomil combination and its efficacy in terms of achieving BP goal in patients with hypertension. Advantages of its use from the patient’s perspective are also discussed.

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Section: Amlodipine/olmesartan Medoxomil: Pharmacokinetics and Mechanmentioning

confidence: 99%

Section: Amlodipine/olmesartan Medoxomil: Pharmacokinetics and Mechanmentioning

confidence: 99%

Critical appraisal of amlodipine and olmesartan medoxomil fixed-dose combination in achieving blood pressure goals

Basile

2010

IBPC

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“…Like other dihydropyridine CCB, amlodipine selectively inhibits calcium (Ca 2+ ) influx across cell membranes in cardiac and vascular smooth muscle with a greater effect on the latter 15. Rohatagi et al16 reported the pharmacokinetics of olmesartan medoxomil and amlodipine besylate alone and in a fixed-dose combination in five phase I crossover studies in healthy volunteers. The similarity of the mean steady-state pharmacokinetics of olmesartan and amlodipine at doses of 40 and 10 mg, respectively, their drug concentration–time curves, and the maximum observed plasma drug concentrations within their prespecified bioequivalence (80%–125%) showed that they were well suited to coadministration in a fixed-dose combination 16.…”

Section: Pharmacodynamics Of Olmesartan and Amlodipinementioning

confidence: 99%

“…Rohatagi et al16 reported the pharmacokinetics of olmesartan medoxomil and amlodipine besylate alone and in a fixed-dose combination in five phase I crossover studies in healthy volunteers. The similarity of the mean steady-state pharmacokinetics of olmesartan and amlodipine at doses of 40 and 10 mg, respectively, their drug concentration–time curves, and the maximum observed plasma drug concentrations within their prespecified bioequivalence (80%–125%) showed that they were well suited to coadministration in a fixed-dose combination 16. Furthermore, coadministration of amlodipine besylate and olmesartan medoxomil, as commercially available separate dosage forms, for 10 days showed no evidence of any negative pharmacokinetic drug–drug interactions 16…”

Section: Pharmacodynamics Of Olmesartan and Amlodipinementioning

confidence: 99%

Role of olmesartan in combination therapy in blood pressure control and vascular function

Ferrario¹

2010

VHRM

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Angiotensin receptor blockers have emerged as a first-line therapy in the management of hypertension and hypertension-related comorbidities. Since national and international guidelines have stressed the need to control blood pressure to <140/90 mmHg in uncomplicated hypertension and <130/80 mmHg in those with associated comorbidities such as diabetes or chronic kidney disease, these goal blood pressures can only be achieved through combination therapy. Of several drugs that can be effectively combined to attain the recommended blood pressure goals, fixed-dose combinations of angiotensin receptor blockers and the calcium channel blocker amlodipine provide additive antihypertensive effects associated with a safe profile and increased adherence to therapy. In this article, we review the evidence regarding the beneficial effects of renin–angiotensin system blockade with olmesartan medoxomil and amlodipine in terms of blood pressure control and improvement of vascular function and target organ damage.

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“…The plasma elimination half-life of Levamlodipine has been found to be 31 ± 13 hrs. Different methods for the determination of Amlodipine in biological fluids, such as gas chromatography (GC) [1] or liquid chromatography (LC) [2][3][4] or mass spectrometric analysis [5][6][7], previously reported methods [8][9][10][11][12] either had long retention time (10-15min) or suffered from low sensitivity and in some cases required large sample injection volumes. Hence the main objective of this work was to develop a simple, sensitive, rapid and reliable mass spectrometry method for the quantification of S-amlodipine in human plasma.…”

Section: Introductionmentioning

confidence: 99%

Determination of S-amlodipine in Human Plasma Using Tizanidine as Internal Standard by Lc/Ms/Ms Method

Durga¹

2015

J Bioanal Biomed

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Table 2: Result of stability, dilution integrity, matrix effect and ruggedness.CPD as an anticoagulant in polypropylene tubes. The stability ranged from 99.1% to 101.3%, which are within limits (Table 2). Stock solution stability at room temperatureStock solution stability at room temperature was performed by storing S-amlodipine and internal standard (Tizanidine) stock solutions at room temperature. The evaluation of stability was done by assaying six replicate injections of appropriately prepared dilutions of stored stock aliquot solutions of S-amlodipine and internal standard (Tizanidine) against six replicate injection of appropriately prepared dilution from fresh stock solutions of S-amlodipine and internal standard (Tizanidine) .The stock solution of S-amlodipine and internal standard (Tizanidine) was found to be stable, when stored at room temperature. The percent stability of the stock solution stability was 97.5% and 103.3% respectively, which are within limits (Table 2). Dilution integrityDilution Integrity was determined by assaying four replicates QCs spiked approximately two times the concentration of ULOQ. Samples were diluted by an appropriate factor (two) prior to extraction, against freshly spiked calibration standard samples. The accuracy for two times diluted concentration was 101.9% and four times diluted concentration were 101.2% for S-amlodipine .The precision for two times diluted concentration were 4.0% and four times diluted concentration were 2.8% for S-amlodipine , which are within limits (Table 2). Matrix effectMatrix effect was calculated by spiking analyte and IS at LQC and HQC levels into each of blank plasma extracts from six different batches of matrix respectively and analyzed in duplicate against six replicate injections of aqueous samples at low and high QCs samples. At low and QCs samples, the % coefficient of variation for matrix factor was found to be 9.35% and 6.84%, respectively for S-amlodipine which is within limits (Table 2). RuggednessThe ruggedness of the extraction procedure and chromatographic method was evaluated by analysis of a batch of six sets of quality control samples and a set of calibration standards using different column (same type) by another analyst. The within batch accuracy ranged from 107.1% to111.4% and within batch precision ranged from 1.8% to 4.7% for S-amlodipine .The results indicated that the batch met the acceptance criteria of linearity, precision and accuracy data of the quality control samples, which are within limits (Table 2). Stock solution stability at refrigerated temperature (4.0 days)Stock solution stability at refrigerated temperature was performed by S-amlodipine and internal standard (Tizanidine) stock solutions at refrigerated temperature. The evaluation of stability was done by assaying six replicates injections of appropriately prepared dilution from stored aliquot solutions of S-amlodipine and internal standard (Tizanidine) against six replicate injection of appropriately prepared dilution from fresh stock solutions of S-am...

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Pharmacokinetics of Amlodipine and Olmesartan After Administration of Amlodipine Besylate and Olmesartan Medoxomil in Separate Dosage Forms and as a Fixed‐Dose Combination

Cited by 28 publications

References 17 publications

Critical appraisal of amlodipine and olmesartan medoxomil fixed-dose combination in achieving blood pressure goals

Critical appraisal of amlodipine and olmesartan medoxomil fixed-dose combination in achieving blood pressure goals

Role of olmesartan in combination therapy in blood pressure control and vascular function

Determination of S-amlodipine in Human Plasma Using Tizanidine as Internal Standard by Lc/Ms/Ms Method

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