Celiprolol, atenolol and propranolol: a comparison of pulmonary effects in asthmatic patients.

Celiprolol, a new beta-adrenoceptor antagonist, blocks serotonin- and methacholine-mediated bronchoconstriction in animals, even in the presence of propranolol. In two, randomized, placebo-controlled, 5-way crossover trials, the pulmonary effects of celiprolol 200 and 400 mg, propranolol 40 mg and atenolol 100 mg were compared in 34 asthmatic patients. Pulmonary function was measured after single doses of each agent, and again following subsequent, graded doses of albuterol or isoproterenol aerosol. Changes in one-second forced expiratory volume (FEV1) and maximal midexpiratory flow rate (FEF25-75) prior to albuterol or isoproterenol were positive after placebo and both doses of celiprolol. Propranolol, and to a lesser extent, atenolol, caused significant reductions in both measures of pulmonary function. Overall changes in FEV1 following each drug plus isoproterenol or albuterol were positive, in the rank order, celiprolol approximately placebo greater than atenolol greater than propranolol. Propranolol pretreatment caused a significant reduction in the effect of bronchodilator. Unlike atenolol and propranolol, celiprolol was highly bronchosparing and did not antagonize sympathomimetic bronchodilators.

Effects of high doses of celiprolol in asthmatic patients.

Sixteen normotensive asthmatic patients received single doses of 400 and 600 mg of celiprolol and 100 mg of atenolol in this placebo-controlled, double-blind crossover study. Pulmonary function was assessed by spirometry. Changes in forced one-second expiratory volume (FEV1) and mid-maximal expiratory flow (MMEF) following both doses of celiprolol were indistinguishable from the effects of placebo, whereas atenolol caused a significant reduction in both measurements of pulmonary function. Graded doses of albuterol, a beta 2-selective sympathomimetic administered at 15-min intervals starting 3 h after each treatment, as expected, caused bronchodilation. The overall bronchodilatory effects of this combined, beta-blocker plus albuterol treatment on pulmonary function were greatest after celiprolol 600 mg, followed in order by celiprolol 400 mg, placebo, and atenolol. Celiprolol 400 mg and 600 mg neither caused bronchoconstriction nor antagonized albuterol in this acute study. Because of its bronchosparing properties, even at high doses, celiprolol may offer an advantage over other, similar agents in the treatment of hypertension and angina in asthmatics.

Bronchosparing properties of celiprolol, a new beta 1, alpha 2-blocker, in propranolol-sensitive asthmatic patients.

The bronchopulmonary effects of celiprolol were studied in 12 male asthmatic patients who showed mean maximum changes of -24% in forced one-second expiratory volume (FEV1) and 130% in airways resistance (Raw) following a single, 80 mg dose of propranolol. Celiprolol 200 and 400 mg and placebo were administered in double-blind, random fashion. Raw and FEV1 were determined by whole body plethysmography 1, 2, and 3 h post dose. For placebo and celiprolol 200 and 400 mg, mean maximum changes in FEV1 were 0.6, 2.8, and 2.4%, and for Raw, 11.3, -0.2, and -10.9%, respectively. Pulmonary effects of the three treatments were indistinguishable but differed significantly from propranolol. Five 0.5 mg doses of terbutaline aerosol, administered at 15-min intervals starting 3 h post drug or placebo, caused less bronchodilation after propranolol than after placebo, or celiprolol 200 or 400 mg; the responses after the latter three were indistinguishable. These results suggest that celiprolol is highly bronchosparing and does not block bronchodilation following the beta 2-agonist terbutaline in propranolol-sensitive asthmatics. In contrast to classical beta-adrenoceptor antagonists, celiprolol may afford a greater margin of safety in asthmatic patients with angina or hypertension.

The bronchosparing effect of celiprolol, a new beta 1- alpha 2-receptor antagonist on pulmonary function of propranolol-sensitive asthmatics.

Twelve normotensive asthmatics who demonstrated bronchoconstriction after a single oral dose of 80 mg of propranolol received (according to a double-blind, randomized, crossover design) placebo, celiprolol 200 mg, and celiprolol 400 mg at intervals of at least three days. Pulmonary function parameters were measured by whole body plethysmography just before treatment and hourly for three hours. Thereafter, terbutaline (0.5 mg), a beta2 agonist, was administered in aerosol form at 15-minute intervals for a total of five doses. This design permitted a safety assessment of the effect of placebo and celiprolol on resting pulmonary function and the evaluation of any interaction between this beta blocker and terbutaline. Propranolol 80 mg produced a statistically significant decrease in a forced one second expiratory volume and forced vital capacity, and a pronounced rise in airways resistance as compared with either dose of celiprolol or with placebo (P less than .001). The effect of celiprolol was not statistically distinguishable from placebo. Terbutaline caused further net bronchodilation after administration of celiprolol and placebo but, even at supratherapeutic doses, failed to restore pulmonary function parameters to baseline levels after treatment with propranolol. The bronchosparing effect of celiprolol may be due to its unique pharmacologic profile, which includes cardioselectivity, modest beta 2-agonist activity, and alpha 2-receptor blockade.