Effects of varying degrees of renal impairment on the pharmacokinetic disposition of nebivolol

Shaw, Andrew; Liu, S.; Zachwieja, L. F.; Eddy, Timothy J.; Donnelly, Charles; Huang, M. Y.

doi:10.1016/j.clpt.2004.12.037

Cited by 5 publications

(12 citation statements)

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“…8,9 The pharmacokinetics of nebivolol by CYP2D6 genotype have been previously evaluated [10][11][12][13][14] and reviewed. 17,18 Nebivolol consists of a racemic mix of equal proportions of the enantiomers d-nebivolol and l-nebivolol. Nebivolol is a selective β 1 -blocker with vasodilatory properties approved for the treatment of hypertension.…”

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confidence: 99%

Effects of Commonly Administered Agents and Genetics on Nebivolol Pharmacokinetics: Drug-Drug Interaction Studies

Lindamood¹,

Ortiz²,

Shaw³

et al. 2011

The Journal of Clinical Pharmacology

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Drug interactions are a significant clinical concern, particularly in patients with conditions such as heart disease and hypertension, in whom coadministration of multiple drugs is common. Nebivolol is a selective β(1)-blocker with vasodilatory properties approved for the treatment of hypertension. Drug-drug interactions were investigated when nebivolol was coadministered to subjects classified as poor CYP2D6 metabolizers and extensive CYP2D6 metabolizers who were receiving other drugs commonly administered to patients with hypertension or compounds metabolized by cytochrome P450 (CYP) 2D6. There were no drug-drug interactions when nebivolol was coadministered with hydrochlorothiazide, furosemide, ramipril, losartan, digoxin, or warfarin. Coadministration with fluoxetine (also metabolized by CYP2D6) in extensive CYP2D6 metabolizers impeded the apparent clearance of nebivolol. The authors conclude that nebivolol is safe and well tolerated regardless of genotype and type of medication coadministered.

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mentioning

confidence: 99%

Effects of Commonly Administered Agents and Genetics on Nebivolol Pharmacokinetics: Drug-Drug Interaction Studies

Lindamood¹,

Ortiz²,

Shaw³

et al. 2011

The Journal of Clinical Pharmacology

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“…Shaw et al . observed a progressive increase in the AUC values of nebivolol as kidney disease progresses. The authors reported AUC values for the isomeric mixture of 6.59 ng.h ml –1 , 4.55 ng.h ml –1 , 11.28 ng.h ml –1 and 23.36 ng.h ml –1 for healthy volunteers and patients with mild, moderate and severe CKD, respectively.…”

Section: Discussionmentioning

confidence: 90%

“…The oral clearance values observed in the CKD group (508.34 l h –1 for l ‐nebivolol and 691.72 l h –1 for d ‐nebivolol) agree with those obtained by Shaw et al . for patients with moderate CKD who received nebivolol as a racemic mixture (738 l h –1 ). Shaw et al .…”

Section: Discussionmentioning

confidence: 99%

Influence of chronic kidney disease and haemodialysis treatment on pharmacokinetics of nebivolol enantiomers

Neves

Lanchote

Neto

et al. 2016

Brit J Clinical Pharma

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AIMThe present study evaluated the pharmacodynamics and pharmacokinetics of nebivolol enantiomers in patients with chronic kidney disease (CKD) and in patients undergoing haemodialysis. METHODSForty-three adult patients were distributed into three groups: healthy volunteers and hypertensive patients with normal kidney function (n = 22); patients with stage 3 and 4 CKD (n = 11); and patients with stage 5 CKD undergoing haemodialysis (n = 10). The subjects received a single oral dose of 10 mg racemic nebivolol. Serial blood samples were collected up to 48 h after administration of the drug and heart rate variation was measured over the same interval during the isometric handgrip test. The nebivolol enantiomers in plasma were analysed by liquid chromatography-tandem mass spectrometry. RESULTSThe pharmacokinetics of nebivolol is enantioselective, with a greater plasma proportion of l-nebivolol. CKD increased the area under the concentration-time curve (AUC) of l-nebivolol (6.83 ng.h ml -1 vs. 9.94 ng.h ml -1 ) and d-nebivolol (4.15 ng.h ml -1 vs. 7.30 ng.h ml -1 ) when compared with the control group. However, the AUC values of l-nebivolol (6.41 ng.h ml -1 ) and d-nebivolol (4.95 ng.h ml -1 ) did not differ between the haemodialysis and control groups. The administration of a single dose of 10 mg nebivolol did not alter the heart rate variation induced by isometric exercise in the investigated patients. CONCLUSIONSStage 3 and 4 CKD increases the plasma concentrations of both nebivolol enantiomers, while haemodialysis restores the pharmacokinetic parameters to values similar to those observed in the control group. No significant difference in heart rate variation induced by isometric exercise was observed between the investigated groups after the administration of a single oral dose of 10 mg nebivolol. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Chronic kidney disease decreases the nonrenal clearance of drugs as a result of the accumulation of uraemic toxins, which reduce the activity of cytochrome P 450 (CYP) isoforms and transporters.• Haemodialysis eliminates uraemic toxins and restores the activity of CYP isoforms. British Journal of Clinical PharmacologyBr J Clin Pharmacol (2016) 82 83-91 83

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“…Because patients on dialysis were not studied, nebivolol should be used with caution in this population. 44 …”

Section: Pharmacokineticsmentioning

confidence: 97%

“…44 Nebivolol does not have to be adjusted in patients with mild and moderate renal impairment. 45 However, a severely impaired patient can expect to experience a 3-to 4-fold increase in exposure levels of nebivolol relative to a normally functioning renal subject after an equal dose of nebivolol, and thus the dosage of nebivolol should be appropriately adjusted in these individuals.…”

Section: Dosing and Administrationmentioning

confidence: 99%

Nebivolol

Sule

Frishman²

2006

Cardiology in Review

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Nebivolol is a beta-blocker under U.S. Food and Drug Administration review for the treatment of hypertension. The unique pharmacologic properties of nebivolol include high specificity for the beta-1 receptor and a nitric oxide-mediated vasodilatory effect. The agent provides significant blood pressure reduction from baseline values as compared with placebo. Clinical trials have demonstrated that nebivolol reduces blood pressure similarly to atenolol, bisoprolol, amlodipine, nifedipine, lisinopril, and hydrochlorothiazide. The tolerability of nebivolol is similar to or better than that of these agents. In elderly patients (> or = 70 years of age) with clinically stable congestive heart failure, the addition of nebivolol to the treatment regimen improved the time to all-cause mortality and cardiovascular hospital admissions over that of placebo. If approved, nebivolol would likely be a viable alternative therapy for hypertension and heart failure; however, additional studies are needed in patients having coronary artery disease.

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Effects of varying degrees of renal impairment on the pharmacokinetic disposition of nebivolol

Cited by 5 publications

References 0 publications

Effects of Commonly Administered Agents and Genetics on Nebivolol Pharmacokinetics: Drug-Drug Interaction Studies

Effects of Commonly Administered Agents and Genetics on Nebivolol Pharmacokinetics: Drug-Drug Interaction Studies

Influence of chronic kidney disease and haemodialysis treatment on pharmacokinetics of nebivolol enantiomers

Nebivolol

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