Pharmacokinetics of the Effect of Nebivolol 5mg on Airway Patency in Patients with Mild to Moderate Bronchial Asthma and Arterial Hypertension A Randomised, Placebo-Controlled Study

摘要

Objective: To evaluate the pharmacokinetics of a single dose of nebivolol 5mg on airway conductance in patients with stable asthma and arterial hypertension.Design: Randomised, double-blind, placebo-controlled, crossover study.Patients: Twelve nonsmokers (five males; mean age 55.2+-11.7 years, range 25 to 71 years) with stable mild to moderate asthma [mean baseline forced expiratory volume in 1 second (FEV_1) 94.3+-16.3%; change in FEV_1 after salbutamol 200mug:19:9 +-4.4% of baseline value] and WHO stage 1-2 mild to moderate arterial hypertension [mean baseline systolic blood pressure (SBP) and diastolic blood pressure (DBP) 158.3+-12.4 and 99.5+-5.8mm Hg, respectively].Main outcome measures and results/Respiratory function (vital capacity, FEV_1, forced vital capacity, peak expiratory flow, forced mid expiratory flow, specific airways resistance) and cardiovascular parameters (SBP, DBP and heart rate) were measured at baseline (to) and at 1 (t_1), 3 (t_3), 6 (t)6), 12 (t_(12)) and 24 (t_(24)) hours after the administration of nebivolol 5mg and placebo. There was a 48- to 72-hour washout period between the two test days. Exhaled nitric oxide (e-NO) was also determined at to, t_6 and t_(24). There was no significant change from baseline in any of the parameters of respiratory function or e-NO throughout the study. Compared with placebo, nebivolol induced a reduction in SBP, which was statistically significant at time t_6 (139.2mm Hg for nebivolol vs 159.6mm Hg for placebo; p < 0.05 for between-group differences) and remained significant until time t24. There was also a significant reduction in DBP at time t_6 (85.0vs 97.5mm Hg; p < 0.05) and t_(12) (89.6 vs 100.8mm Hg; p < 0.05) in patients receiving nebivolol versus placebo.Conclusions: From our results in a small group of patients with hypertension and stable mild to moderate asthma, nebivolol does not appear to affect airway patency even during peak antihypertensive efficacy, thus suggesting a favourable tolerability profile in the presence of reversible airway obstruction.