| Pharmacokinetic study and cardiovascular monitoring of nebivolol in normal and obese subjects. | |
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MedLine Citation:
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PMID: 9112066 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: The pharmacokinetics of a single i.v. dose of the new racemic beta-adrenoceptor-blocker nebivolol [0.073 mg base.kg-1 ideal body weight (IBW)] was studied in 9 obese (157% IBW) and 9 non-obese healthy volunteers (98% IBW). Each group contained 4 men and 5 women, aged 32 years, including one poor hydroxylator (dextrometorphan test). METHODS: The cardiovascular effects of nebivolol are significant decreases in systolic and diastolic blood pressure, heart rate and cardiac output, which last up to 4-5 h. The plasma concentrations of the separate d- and l- enantiomers of nebivolol, with and without hydroxylated metabolite, were measured by radioimmunoassay and the unchanged racemate by high-pressure liquid chromatography (HPLC). The pharmacokinetic parameters for each form were calculated separately. RESULTS: The main pharmacokinetic parameters of unchanged nebivolol in extensive metabolizers were (controls): distribution volume at steady state (Vss) 673 l; volume corrected by real body weight (Vss.kg-1) 11.2 l.kg-1; total clearance (CL) 51.6 h-1; and terminal half-life (t1/2) 10.3 h. The Vss (898 l) and CL (71.6 l.h-1) were significantly higher in obese patients. But Vss.kg-1 (9.4 l.kg-1) and t1/2 (10.0 h) were not significantly different from those in controls. The CL was clearly reduced (15-18 l.h-1) and the t1/2 prolonged (32-34 h) in poor hydroxylators, in both control and obese subjects. The pharmacokinetic parameters of the separate unchanged enantiomers were similar to those of the racemate in both groups. The pharmacokinetics of l-nebivolol were more influenced by the hydroxylation phenotype than those of d-nebivolol. The trend of the results for the sum of each enantiomer plus its metabolite, was similar to those for the unchanged form. CONCLUSION: The distribution of nebivolol in the adipose tissue in obese subjects is limited, despite its high lipophilicity. The differences between obese and non-obese subjects were not clinically relevant. |
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Authors:
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G Cheymol; R Woestenborghs; E Snoeck; R Ianucci; J P Le Moing; L Naditch; J C Levron; J M Poirier |
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Publication Detail:
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Type: Clinical Trial; Comparative Study; Journal Article |
Journal Detail:
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Title: European journal of clinical pharmacology Volume: 51 ISSN: 0031-6970 ISO Abbreviation: Eur. J. Clin. Pharmacol. Publication Date: 1997 |
Date Detail:
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Created Date: 1997-06-26 Completed Date: 1997-06-26 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 1256165 Medline TA: Eur J Clin Pharmacol Country: GERMANY |
Other Details:
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Languages: eng Pagination: 493-8 Citation Subset: IM |
Affiliation:
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Service de Pharmacologie, Hôpital St Antoine, Paris, France. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adrenergic beta-Antagonists
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pharmacokinetics*,
pharmacology* Adult Benzopyrans / pharmacokinetics*, pharmacology* Blood Pressure / drug effects Cardiac Output / drug effects Chromatography, High Pressure Liquid Ethanolamines / pharmacokinetics*, pharmacology* Female Half-Life Heart Rate / drug effects Humans Lipids / blood Male Obesity / metabolism*, physiopathology* |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic beta-Antagonists; 0/Benzopyrans; 0/Ethanolamines; 0/Lipids; 99200-09-6/nebivolol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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