A comparison of the pharmacokinetics of propranolol in obese and normal volunteers.

Bowman, S.L.; Hudson, S. A.; Simpson, G M; Munro, JF; Clements, J. A.

doi:10.1111/j.1365-2125.1986.tb02837.x

Cited by 58 publications

(36 citation statements)

References 10 publications

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“…In contrast to expected decreases in bioavailability associated with increased splanchnic blood flow in obesity, 23 the bioavailability of midazolam 13 and propanolol, 14 two compounds with moderate to high hepatic extraction, was shown not to be significantly different between obese and lean individuals. Body weight was shown to have no effect on the bioavailability of cyclosporine in renal transplant recipients.…”

Section: Obesity and Drug Absorptioncontrasting

confidence: 71%

Pharmacokinetic Considerations in Obesity

Blouin

Warren

1999

Journal of Pharmaceutical Sciences

183

132

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Section: Obesity and Drug Absorptioncontrasting

confidence: 71%

Pharmacokinetic Considerations in Obesity

Blouin

Warren

1999

Journal of Pharmaceutical Sciences

183

132

View full text Add to dashboard Cite

“…Only six studies have directly compared the oral bioavailability and absorption rate of drugs between obese and nonobese subjects on the basis of both oral and intravenous administration (80)(81)(82)(83)(84)(85). For propranolol, clearance (CL) after an intravenous dose was not different between six obese (136 ± 36 kg) and six control (67 ± 5 kg) subjects.…”

Section: The Influence Of Obesity On Oral Bioavailability and Absorptmentioning

confidence: 99%

Drug Disposition in Obesity: Toward Evidence-Based Dosing

Knibbe

Brill

Rongen

et al. 2015

Annu. Rev. Pharmacol. Toxicol.

107

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Obesity and morbid obesity are associated with many physiological changes affecting pharmacokinetics, such as increased blood volume, cardiac output, splanchnic blood flow, and hepatic blood flow. In obesity, drug absorption appears unaltered, although recent evidence suggests that this conclusion may be premature. Volume of distribution may vary largely, but the magnitude and direction of changes seem difficult to predict, with extrapolation on the basis of total body weight being the best approach to date. Changes in clearance may be smaller than in distribution, whereas there is growing evidence that the influence of obesity on clearance can be predicted on the basis of reported changes in the metabolic or elimination pathways involved. For obese children, we propose two methods to distinguish between developmental and obesity-related changes. Future research should focus on the characterization of physiological concepts to predict the optimal dose for each drug in the obese population.

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“…The results for the normal volunteers look for correlations between distribution volume and were similar to those reported for propranolol by Castleden physicochemical parameters. The V ss values for sotalol were et al [26] and Bowman et al [27], and for labetalol by Elliot 81.0±12.3 in obese subjects and 70.8±11.6 l in controls; et al [28] and Abernethy et al [29)]. Some pharmacokinetic those for bisoprolol were 173.0±35.2 (obese) and parameters were obtained for nebivolol by Van Peer et al…”

Section: =090; P=001 Coefficients the Zwitterionic (±) Character Omentioning

confidence: 99%

Pharmacokinetics of β‐adrenoceptor blockers in obese and normal volunteers

Cheymol

Poirier

Carrupt

et al. 1997

Brit J Clinical Pharma

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Aims Obesity can modify the pharmacokinetics of lipophilic drugs. As b-adrenoceptor blockers (BB) are often prescribed for obese patients suffering from hypertension or coronary heart disease, this study compares the pharmacokinetics of lipophilic b-adrenoceptor blockers in obese and control subjects. Methods Nine obese (157±24% of ideal body weight (IBW) mean±s.d.) and nine non-obese healthy volunteers (98±10% IBW), aged 32±9 years, were included in the study. Subjects were randomly given a single i.v. infusion of one of the following racemic b-adrenoceptor blockers, whose doses (expressed as base per kg of IBW) were: propranolol (0.108 mg), labetalol (0.99 mg) and nebivolol (0.073 mg ). The plasma concentrations of unchanged drugs were measured by h.p.l.c. The ionisation constants and lipophilicity parameters of b-adrenoceptor blockers were assessed. Results The pharmacokinetic data for the three drugs were qualitatively similar. There was a trend towards a greater total distribution volume (V ss ) in obese patients than in controls. However, V ss expressed per kg body weight was slightly smaller in obese patients. The relationship between V ss and lipophilicity of five b-adrenoceptor was studied by combining the current results with those previously obtained with a moderately lipophilic drug (bisoprolol ) and a hydrophilic one (sotalol). The V ss of the five drugs was positively and well-correlated (r 2 =0.90; P<0.01) with their distribution coefficient at pH 7.4 (log D 7.4 ), but not with their partition coefficients. The linear regression coefficients for lean and obese subjects were very similar. Conclusions Lipophilic b-adrenoceptor blockers seem to diffuse less into adipose than into lean tissues. All electrical forms of the drugs (i.e. cations, neutral forms, or zwitterions) present at physiological pH contribute to their tissue distribution, in both obese and lean subjects.Their tissue distribution in obese patients could be restricted by the sum of hydrophobic forces and hydrogen bonds they elicit with macromolecules in lean tissues.

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A comparison of the pharmacokinetics of propranolol in obese and normal volunteers.

Cited by 58 publications

References 10 publications

Pharmacokinetic Considerations in Obesity

Pharmacokinetic Considerations in Obesity

Drug Disposition in Obesity: Toward Evidence-Based Dosing

Pharmacokinetics of β‐adrenoceptor blockers in obese and normal volunteers

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