Osmotic Release Oral Drug Delivery System of Metoprolol in Hypertensive Asthmatic Patients: Pharmacodynamic Effects on β2-Adrenergic Receptors

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 1994-09, Vol.24 (3), p.339-346
• Main Authors: Bauer, Karin, Kaik, Gerhard, Kaik, Brigitte
• Format: Article
• Language: English
• Subjects: Antihypertensive agents; Biological and medical sciences; Cardiovascular system; Medical sciences; Pharmacology. Drug treatments
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.24.3.339

This study investigated the effects of an osmotic release oral drug delivery system of metoprolol on the changes induced by cumulative doses of inhaled salbutamol on bronchomotor tone, skeletal muscle, and the circulatory system after single (day 1) and multiple (day 7) dosing in 18 hypertensive asthmatic patients (forced expiratory volume in 1 second >50% predicted; diastolic blood pressure >90 mm Hg). The patients were given 14/190 mg metoprolol, 100 mg atenolol, and placebo once daily for a 7-day period each in a randomized, double-blind, crossover design. At the estimated time of peak plasma concentrations, cumulative doses of salbutamol (12.5, 37.5, 112.5, 412.5, 812.5, and 1612.5 μg) were applied every 20 minutes. Specific airway conductance, finger tremor amplitude, heart rate, and blood pressure were registered at baseline and at each dose increment. The slopes of the salbutamol dose-response curves of specific airway conductance did not differ on day 1 (P>.05). On day 7, atenolol caused a shift of the dose-response curves of specific airway conductance to the right (P