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

Abstract

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.

Pharmacokinetic Parameters and Over-Responsiveness of Iranian Population to Propranolol

“…In the study conducted in Poland, the volume of distribution of propranolol was 5±1.2 L/kg, which was within the range of volume of distribution obtained in our study. 33 In another study conducted in Malaysia by Zain-Hamid R and colleagues, volume of distribution following a single 20 mg dose of propranolol was 543.89±292.91 L which was more than the results from our study. 34 Although in our study pharmacokinetic parameters of propranolol were examined as a single dose, but it has shown that the value of distribution with repeated doses decreases due to saturated tissue attachment of the drug.…”

Hypertension in Obesity and the Impact of Weight Loss

“…In an in vivo study directly measuring renal hemodynamics, obese patients had a greater renal vasodilatory response to short term angiotensin converting enzyme inhibition with captopril than normal-weight individuals [51]. Although there are no measurable changes in pharmacokinetic handling of beta blockers in obesity [52], another study demonstrated that obese patients had significantly greater blood pressure response compared to lean patients after treatment with combined alpha- and beta-adrenergic blockade [53]. We recently performed an observational study evaluating the renal effects of time-updated exposure to renin-angiotensin system blockade compared to any other antihypertensive therapy in over 200,000 obese, non-diabetic, hypertensive patients in the United Kingdom.…”

The Impact of Obesity on the Pharmacology of Medications Used for Cardiovascular Risk Factor Control

“…For lipophilic agents, clearance can be unchanged/decreased (propranolol 23,24,39,40,42 ) or increased (metoprolol, 43 nebivolol 41 ). Because these drugs are primarily hepatically cleared this finding potentially reflects alterations in metabolic reactions and enzymes.…”