Pharmacokinetic study and cardiovascular monitoring of nebivolol in normal and obese subjects

Cheymol, G; Woestenborghs, Robert; Snoeck, Eric; Ianucci, R; Moing, J.P. Le; Naditch, Lisa; Levron, Jean-Claude; Poirier, Jean‐Marie

doi:10.1007/s002280050237

Cited by 51 publications

(31 citation statements)

References 9 publications

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“…The results of pharmacokinetic studies for the healthy controls were similar to those reported by other investigators [11][12][13]. In obese subjects both with and without hyperlipidaemia the pharmacokinetics of propranolol and atenolol were altered, most significantly during the elimination phases.…”

Section: Discussionsupporting

confidence: 87%

“…Contrary to our observations, Cheymol et al [12] reported an increased clearance of nebivolol in obesity. Nevertheless, the results of Galletti et al [11] suggested that obesity did not influence the pharmacokinetics of water-soluble b-blockers.…”

Section: Discussioncontrasting

confidence: 83%

“…The variability in lipophilicity could further influence their pharmacokinetics and consequent haemodynamic effects of those drugs in obese patients [9,10]. In the relatively few studies on the kinetics ofblockers in obese patients the authors did not investigate concomitant lipid disorders [11][12][13]. Our previous data suggested that lipid status could influence both the pharmacokinetics and pharmacodynamics of propranolol in hyperlipidaemia [7,14].…”

Section: Introductionmentioning

confidence: 99%

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Comparative pharmacokinetics and pharmacodynamics of propranolol and atenolol in normolipaemic and hyperlipidaemic obese subjects

Wójcicki

Jaroszynska

Droździk

et al. 2003

Biopharm & Drug Disp

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The lipophilic beta-adrenoreceptor antagonist propranolol and hydrophilic atenolol have been studied to define their pharmacokinetic and pharmacodynamic characteristics in obese patients. A total of 43 subjects were allocated into three study groups: (1) healthy, lean, normolipaemic volunteers, (2) obese normolipaemic subjects, and (3) obese patients with lipid disorders. A crossover method with an interval of 2 weeks was applied for oral 80 mg propranolol and oral 100 mg atenolol administration. Heart rate as well as systolic and diastolic blood pressure were recorded during 24 h. At each time-point of measurement blood serum concentration of propranolol and atenolol were evaluated. Pharmacokinetic parameters of the drugs were calculated using a one-compartment open model for extravascular administration. There were no statistically significant differences in blood serum concentrations of propranolol between the studied groups. The concentrations of atenolol were significantly lower in both normolipaemic and hyperlipidaemic obese subjects. A trend towards increase in Vd/F and Cl/F of propranolol in obese patients with hyperlipidaemia were noted. In the case of water-soluble atenolol, the AUC, C(max), Cl/(F x BW) were significantly lower in obese hyperlipidaemic and normolipaemic patients in comparison with lean subjects. The pharmacodynamic effects of propranolol and atenolol in obese and lean subjects were of similar magnitude. The observed differences between obese and non-obese persons were clinically not relevant.

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Section: Discussionsupporting

confidence: 87%

Section: Discussioncontrasting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

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Comparative pharmacokinetics and pharmacodynamics of propranolol and atenolol in normolipaemic and hyperlipidaemic obese subjects

Wójcicki

Jaroszynska

Droździk

et al. 2003

Biopharm & Drug Disp

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“…110 However, in poor metabolizers taking metoprolol, the lower S/R ratio leads to less ␤-blockade relative to plasma levels, 111 which tends to cancel the effect of the increased plasma levels of both isomers that is related to the lower oxidation rate. Clinically important stereoselective metabolism does not occur for bisoprolol, 112 nebivolol, 113 or bucindolol (D. Ward, personal communication, 1999).…”

Section: Pharmacokinetic Issuesmentioning

confidence: 99%

β-Adrenergic Receptor Blockade in Chronic Heart Failure

2000

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“…The decrease in CYP2D6 activity in human hepatocytes with excess fat may be due to a decreased mRNA level of this gene. On the contrary, Cheymol et al 42 showed increased CYP2D6 activity in obese subjects; nebivolol was used as a CYP2D6 substrate.…”

Section: Subfamily Of the Cyp2d Enzymementioning

confidence: 99%

Effects of obesity on liver cytochromes P450 in various animal models

Tománková¹,

Anzenbacher²,

Anzenbacherová³

2017

BIOMED PAP

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aThe prevalence of obesity and other obesity-related diseases is increasing worldwide. Obesity is a disease characterized by increased body weight, or a condition resulting from excessive accumulation of body fat. Due to increased body fat deposits, obesity has also been associated with increased mortality resulting from higher incidence rates of hypertension, diabetes, or various types of cancer, such as breast, colorectal, cervical and prostate cancer. Physiological changes associated with obesity are likely to result in altered drug biotransformation. The main enzymes enabling the oxidative biotransformation of most drugs are cytochromes P450 (CYPs). The review summarizes how pathophysiological factors, especially obesity, affect properties (e.g. enzyme activity, protein expression, gene expression) of CYP enzymes in various experimental models of human obesity. Results reported by various authors suggest that obesity is associated with a decrease of CYP activities (except for the CYP2C and CYP2E1 enzymes). The only exception is mouse obesity induced by monosodium glutamate (administered to newborn mice) as it usually leads to increased CYP expression. Selecting an animal model that is as close as possible to the properties of human obesity is of paramount importance.

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Pharmacokinetic study and cardiovascular monitoring of nebivolol in normal and obese subjects

Abstract: 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.

Cited by 51 publications

References 9 publications

Comparative pharmacokinetics and pharmacodynamics of propranolol and atenolol in normolipaemic and hyperlipidaemic obese subjects

Comparative pharmacokinetics and pharmacodynamics of propranolol and atenolol in normolipaemic and hyperlipidaemic obese subjects

β-Adrenergic Receptor Blockade in Chronic Heart Failure

Effects of obesity on liver cytochromes P450 in various animal models

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