Document Detail


Pharmacokinetic study and cardiovascular monitoring of nebivolol in normal and obese subjects.
MedLine Citation:
PMID:  9112066     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Clinical Trial; Comparative Study; Journal Article    
Journal Detail:
Title:  European journal of clinical pharmacology     Volume:  51     ISSN:  0031-6970     ISO Abbreviation:  Eur. J. Clin. Pharmacol.     Publication Date:  1997  
Date Detail:
Created Date:  1997-06-26     Completed Date:  1997-06-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1256165     Medline TA:  Eur J Clin Pharmacol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  493-8     Citation Subset:  IM    
Affiliation:
Service de Pharmacologie, Hôpital St Antoine, Paris, France.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-Antagonists / 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:
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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