Bioequivalence of two atenolol formulations in healthy volunteers. Evaluation and prediction of effect kinetics at beta-adrenoceptors in vivo by means of a radioreceptor assay

• Published in: Methods and findings in experimental and clinical pharmacology Vol. 13; no. 2; p. 129
• Main Authors: Sitzler, G, Heibel, B, Lücker, P W, Palm, D
• Format: Journal Article
• Language: English
• Published: Spain 01-03-1991
• Subjects: Adolescent; Adrenergic beta-Antagonists - pharmacology; Adult; Atenolol - administration & dosage; Atenolol - pharmacokinetics; Atenolol - pharmacology; Chromatography, Gas; Double-Blind Method; Heart Rate - drug effects; Humans; Male; Propanolamines - pharmacology; Radioligand Assay; Random Allocation; Receptors, Adrenergic, beta - drug effects; Therapeutic Equivalency
• ISSN: 0379-0355

Pharmacokinetic and pharmacodynamic effects of single oral doses of 200 mg of two atenolol formulations (Tenormin, atenolol (T) and Duraatenolol, atenolol (D)) were assessed in eight male healthy volunteers for 48 h (double-blind crossover design). Both formulations were bioequivalent in terms of pharmacokinetic parameters (AUC, tmax, Cmax, t1/2) as detected by gas liquid chromatography. By means of a radioreceptor assay (RRA) any significant contribution of beta 2-adrenoceptors and active metabolites to effects observed in vivo was ruled out. Based on parameters derived from RRA a prediction of the time course of any beta 1-adrenoceptor-mediated effect in vivo was made. During the first 12 h after intake of atenolol (T) and atenolol (D) effect kinetics simulated from RRA data corresponded very well to the inhibition of exercise-induced tachycardia observed in vivo. Thus, RRA is an in vitro method enabling assessment and prediction of relative bioequivalence of 2 atenolol formulations in vivo. Moreover, it enables establishment of a causal relationship between pharmacodynamic and pharmacokinetic parameters.