Nebivolol

Baldwin, Claudine M; Keam, Susan J.

doi:10.2165/1120274-000000000-00000

Cited by 14 publications

(8 citation statements)

References 35 publications

(86 reference statements)

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Section: Introductionmentioning

confidence: 99%

“…Nebivolol is a cardioselective third-generation β–blocker widely used for the treatment of hypertension [ 1 , 2 ]. In Europe, nevibolol is also indicated for stable mild and moderate chronic heart failure in combination with standard drug therapies in patients aged 70 years and over [ 2 ]. This beta-blocker has a dual mechanism of action, namely it is both highly β1-selective and promotes endothelium-dependent vasodilation [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

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Phenotypic differences in nebivolol metabolism and bioavailability in healthy volunteers

Briciu

Neag

Bocşan

et al. 2015

Medicine and Pharmacy Reports

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IntroductionNebivolol, a third-generation β-blocker, is subject to extensive first-pass metabolism and produces active β-blocking hydroxylated metabolites, like 4-OH-nebivolol. It is primarily a substrate of CYP2D6, a metabolic pathway that is under polymorphic genetic regulation. The objective of this study was to assess the metabolizer phenotype and to evaluate the interphenotype bioavailability and metabolism of nebivolol.Material and methodsForty-three healthy volunteers were included in this open-label, non-randomized clinical trial and each volunteer received a single dose of 5 mg nebivolol. Non-compartmental pharmacokinetic analysis was performed to determine the pharmacokinetic parameters of nebivolol and its active metabolite. The phenotypic distribution was assessed based on the AUC (aria under the curve) metabolic ratio of nebivolol/4-OH-nebivolol and statistical analysis. An interphenotype comparison of nebivolol metabolism and bioavailability was performed based on the pharmacokinetic parameters of nebivolol and its active metabolite.ResultsNebivolol/4-OH-nebivolol AUC metabolic ratios were not characterized by a standard normal distribution. The unique distribution emphasized the existence of two groups and the 43 healthy volunteers were classified as follows: poor metabolizers (PMs)=3, extensive metabolizers (EMs)=40. The phenotype had a marked impact on nebivolol metabolism. The exposure to nebivolol was 15-fold greater for PMs in comparison to EMs.Conclusion40 EMs and 3 PMs were differentiated by using the pharmacokinetic parameters of nebivolol and its active metabolite. The study highlighted the existence of interphenotype differences regarding nebivolol metabolism and bioavailability.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Phenotypic differences in nebivolol metabolism and bioavailability in healthy volunteers

Briciu

Neag

Bocşan

et al. 2015

Medicine and Pharmacy Reports

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“…Nebivolol, a third‐generation β‐blocker with high selectivity for β 1 ‐adrenergic receptors and unique antioxidant effects, has proven to be highly effective in treating hypertension 9, 10, 11. Nebivolol exhibits unique properties that distinguish it from other β‐blockers.…”

Section: Introductionmentioning

confidence: 99%

Nebivolol, But Not Metoprolol, Treatment Improves Endothelial Fibrinolytic Capacity in Adults With Elevated Blood Pressure

Stauffer

Dow

Diehl

et al. 2017

JAHA

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BackgroundVascular endothelial fibrinolytic function is impaired in adults with prehypertension and hypertension and plays a mechanistic role in the development of atherothrombotic events. The influence of β‐blockers on endothelial fibrinolysis is unknown. This study compared the effects of chronic nebivolol and metoprolol treatment on endothelial tissue‐type plasminogen activator (t‐PA) release in adults with elevated blood pressure (BP).Methods and ResultsForty‐four middle‐aged adults (36% women) with elevated BP completed a 3‐month, double‐blind, randomized, placebo‐controlled trial comparing nebivolol (5 mg/d), metoprolol succinate (100 mg/d), and placebo. Net endothelial t‐PA release was determined in vivo in response to intrabrachial infusions of bradykinin and sodium nitroprusside before and after each intervention. In a subset, the dose‐response curves to bradykinin and sodium nitroprusside were repeated with a coinfusion of the antioxidant vitamin C. At baseline, resting BP and endothelial t‐PA release were comparable between the 3 groups. BP decreased to a similar extent (≈10 mm Hg) in the nebivolol‐ and metoprolol‐treated groups. There was a substantial increase (≈30%; P<0.05) in the capacity of the endothelium to release t‐PA following chronic treatment with nebivolol but not metoprolol or placebo. Mitigating oxidant stress with vitamin C coinfusion potentiated t‐PA release (90%; P<0.05) at baseline in all groups. However, after the intervention, t‐PA release was unchanged by vitamin C coinfusion in the nebivolol group only.ConclusionsNebivolol but not metoprolol improves endothelial t‐PA release in adults with elevated BP. This may be an important vascular benefit of nebivolol.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01595516.

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“…Nebivolol is a highly lipophilic, third-generation beta-blocker used for the treatment of hypertension and chronic heart failure (HF) (1,2). Until now, it was proved to possess the highest selectivity for the β1-adrenergic receptors (up to 320-fold vs β2) among the beta-blockers.…”

Section: Introductionmentioning

confidence: 99%

“…Nebivolol is rapidly absorbed after oral administration and food intake has a minimal impact on this process (2,4). According to a study performed on rats, the low bioavailability of nebivolol is due to first-pass metabolism through the gut (8).…”

Section: Introductionmentioning

confidence: 99%

Investigation of a Potential Pharmacokinetic Interaction Between Nebivolol and Fluvoxamine in Healthy Volunteers

et al. 2017

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-PURPOSE:To investigate whether fluvoxamine coadministration can influence the pharmacokinetic properties of nebivolol and its active hydroxylated metabolite (4-OH-nebivolol) and to assess the consequences of this potential pharmacokinetic interaction upon nebivolol pharmacodynamics. METHODS:This open-label, non-randomized, sequential clinical trial consisted of two periods: Period 1 (Reference), during which each volunteer received a single dose of 5 mg nebivolol and Period 2 (Test), when a combination of 5 mg nebivolol and 100 mg fluvoxamine was given to all subjects, after a 6-days pretreatment regimen with fluvoxamine (50-100 mg/day). Non-compartmental analysis was used to determine the pharmacokinetic parameters of nebivolol and its active metabolite. The pharmacodynamic parameters (blood pressure and heart rate) were assessed at rest after each nebivolol intake, during both study periods. RESULTS: Fluvoxamine pretreatment increased C max and AUC 0-∞ of nebivolol (C max : 1.67 ± 0.690 vs 2.20 ± 0.970 ng/mL; AUC 0-∞ : 12.1 ± 11.0 vs 19.3 ± 19.5 ng*h/mL ) and of its active metabolite (C max : 0.680 ± 0.220 vs 0.960 ± 0.290 ng/mL; AUC 0-∞ : 17.6 ±20.1 vs 25.5 ± 29.9 ng*h/mL). Apart from C max , AUC 0-t and AUC 0-∞ , the other pharmacokinetic parameters (t max , k el and t ½ ) were not significantly different between study periods. As for the pharmacodynamic analysis, decreases in blood pressure and heart rate after nebivolol administration were similar with and without fluvoxamine concomitant intake. CONCLUSIONS: Due to enzymatic inhibition, fluvoxamine increases the exposure to nebivolol and its active hydroxylated metabolite in healthy volunteers. This did not influence the blood pressure and heart-rate lowering effects of the beta-blocker administered as single-dose. However, more detail studies involving actual patients are required to further investigate the clinical relevance of this drug interaction.

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Nebivolol

Cited by 14 publications

References 35 publications

Phenotypic differences in nebivolol metabolism and bioavailability in healthy volunteers

Phenotypic differences in nebivolol metabolism and bioavailability in healthy volunteers

Nebivolol, But Not Metoprolol, Treatment Improves Endothelial Fibrinolytic Capacity in Adults With Elevated Blood Pressure

Investigation of a Potential Pharmacokinetic Interaction Between Nebivolol and Fluvoxamine in Healthy Volunteers

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