Controlled-release metoprolol compared with atenolol in asthmatic patients: interaction with terbutaline

The beta 2-adrenoceptor mediated effects on ventilatory capacity, forced expiratory volume in one second (FEV1), forced ventilatory capacity (FVC), heart rate, and skeletal muscle tremor of a new controlled-release (CR) formulation of metoprolol, 100 mg and 200 mg, and of atenolol tablets, 100 mg, were studied in eight asthmatic patients. The effects of single-dose treatment, including placebo as reference, were studied in a randomized, double-blind, cross-over design. Starting 2 h after drug intake, four intravenous infusions containing increasing doses of terbutaline were given at 30-min intervals, followed by three doses of terbutaline inhalations. Maximum plasma concentrations for both metoprolol and atenolol were achieved within the study period. The FEV1 measurements after terbutaline infusions and inhalations were significantly lower after atenolol than after either dose of metoprolol CR. This indicates less blockade of beta 2-adrenoceptors with metoprolol CR than with atenolol at maximum plasma concentrations. The terbutaline-induced skeletal muscle tremor and increase in heart rate were less after atenolol than after either dose of metoprolol CR, also suggesting less interaction of metoprolol CR with beta 2-receptors. Thus, the new CR formulation of metoprolol caused fewer adverse effects on beta 2-adrenoceptor mediated bronchodilatation than a clinically equivalent dose of atenolol.