Pulmonary effects of long-term β2-blockade in healthy subjects: Comparative study of metoprolol OROS

Abstract The effects on airway response of metoprolol OROS (oral osmotic) and three other long-acting β-adrenoceptor blockers were studied. This was a placebo-controlled, randomized, five-period, single-blind, crossover trial in 15 healthy volunteers. Bronchial β-blockade was estimated as the displacement of the salbutamol bronchodilator response of specific airway conductance (SGAW) measured by whole-body plethysmography. Metoprolol OROS ( 14 190 mg ), slow-release (SR) metoprolol (200 mg), atenolol (100 mg), long-acting (LA) propranolol (160 mg), and placebo were given once daily for 7 days. Inhaled salbutamol was administered at peak drug levels in cumulative doses of 12.5 to 800 μg on day 5 and in a single dose of 400 μg on day 7. On day 5, salbutamol induced significant increases in SGAW in each treatment group. SGAW increased after the single dose of salbutamol on day 7 in all groups and then declined steadily. The highest values were found after placebo and metoprolol OROS, with smaller increases after SR metoprolol, atenolol, and LA propranolol, the latter showing the smallest increase. Therefore, it would appear that under steady-state conditions, β 2 -bronchial receptors are least blocked by metoprolol OROS, followed by SR metoptolol, atenolol, and LA propranolol.