Comparative pharmacokinetics and pharmacodynamics of propranolol and atenolol in normolipaemic and hyperlipidaemic obese subjects.
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.
Wójcicki
Jerzy
J
Department of Experimental and Clinical Pharmacology, Pomeranian Academy of Medicine, Szczecin, Poland.
Jaroszynska
Maria
M
Droździk
Marek
M
Pawlik
Andrzej
A
Gawrońska-Szklarz
Barbara
B
Sterna
Rozalia
R
D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D000328:Adult; D019540:Area Under Curve; D001262:Atenolol / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D005260:Female; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D011433:Propranolol / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D001262:Atenolol; D011433:Propranolol