Comparison of nebulized glycopyrrolate and metaproterenol in chronic obstructive pulmonary disease

Abstract

We assessed the bronchodilating effect of glycopyrrolate (GP) and compared it with that of metaproterenol (MP), alone and in combination (GP+MP), in patients with chronic obstructive pulmonary disease (COPD).In a double-blind study, 11 patients (aged (mean±SD) 69±6 yrs; forced expiratory volume in one second (FEV1) 1.2±0.4 L) with stable COPD inhaled nebulized GP 1.0 mg, MP 15 mg, or GP 1.0 mg + MP 15 mg. Spirometry was performed before inhalation and at hourly intervals for 8 h after inhalation.It was found that GP produced a bronchodilating effect that was about equal to that of MP but lasted longer (8 vs 5 h). The combination of GP and MP produced a bronchodilating effect that was greater than that of either drug alone and was evident mostly during the effect of MP. The mean peak percentage improvement in FEV1 over baseline was 35% for GP+MP and 25% for either drug alone.These data suggest that nebulized glycopyrrolate is an effective bronchodilator in some patients with chronic obstructive pulmonary disease. Concurrent administration of glycopyrrolate and metaproterenol produces additional bronchodilation that is primarily apparent during the bronchodilator effect of metaproterenol. Eur Respir J., 1996, 9, 100- Glycopyrrolate (GP), a quarternary ammonium compound, is an anticholinergic agent that has primarily been used with anaesthesia to reduce gastric acidity and salivary secretions or to reverse neuromuscular blockade [1]. Recently, GP has been used as a bronchodilator in patients with asthma [2][3][4][5]. This study was designed to investigate the bronchodilator effect of GP in patients with stable chronic obstructive pulmonary disease (COPD) and compare it with that of another commonly used bronchodilator, the β-adrenergic agonist metaproterenol (MP). In addition, we examined whether the concurrent administration of GP and MP provided any further bronchodilation than GP alone in this group of patients. MethodsEleven men with diagnoses of chronic bronchitis, emphysema, or both [6] were recruited from out-patient pulmonary clinics to participate in the study (table 1). Stability of their disease was defined as no hospitalizations or change in therapy over a 6 month period prior to the study. All patients had a forced expiratory volume in one second/forced vital capacity ratio (FEV1/FVC) of less than 70%, and a history of cigarette smoking. A positive bronchodilator response following inhalation of metaproterenol, as defined by the American Thoracic Society (ATS) criteria [6], was documented during previous pulmonary function testing. None of the subjects had a history of bronchial asthma or were on oral steroids. The study was approved by the institutional review committee and informed consent was obtained from all patients.Measurements of FVC and FEV1 were performed on a Collins Eagle One spirometer (Braintree, MA, USA). The medications were mixed with normal saline to a total volume of 7.5 mL and aerosolized using a Misty-Neb nebulizer (Airlife) with a flow rate of 10 L·min -1 delivered over ...

Pharmacological characterization of the muscarinic receptor antagonist, glycopyrrolate, in human and guinea‐pig airways

“…In normal subjects, glycopyrrolate produces significant bronchodilation of long duration ( Gal & Suratt, 1981 ; Gal et al ., 1984 ). In patients with chronic obstructive pulmonary disease, inhaled nebulized glycopyrrolate (1 mg) produced a bronchodilating effect that lasted for 8 h ( Tzelepis et al ., 1996 ). Similarly, in patients with asthma, when compared to placebo, metered‐dose aerosols of glycopyrrolate (doses ranging from 100–1200 mg) elicited significantly greater bronchodilation that was noted within 30 min of dosing and was sustained for at least 8–12 h ( Walker et al ., 1987 ; Schroeckenstein et al ., 1988 ).…”

“…Glycopyrrolate, a quaternary ammonium compound, is a muscarinic receptor antagonist which has been used in pre‐anaesthetic medication to reduce gastric acid and salivary secretions or to reverse neuromuscular blockade ( Norgaard et al ., 1970 ; Mirakhur & Dundee, 1983 ). Recently, glycopyrrolate has been used as a bronchodilator in patients with asthma and COPD ( Walker et al ., 1987 ; Gilman et al ., 1990 ; Tzelepis et al ., 1996 ). In this study we have investigated the potency and duration of action of glycopyrrolate in inhibiting cholinergic contractile responses evoked by electrical field stimulation (EFS) in guinea‐pig, and human airways.…”

Pharmacokinetics of Co‐Suspension Delivery Technology Budesonide/Glycopyrronium/Formoterol Fumarate Dihydrate (BGF MDI) and Budesonide/Formoterol Fumarate Dihydrate (BFF MDI) Fixed‐Dose Combinations Compared With an Active Control: A Phase 1, Randomized, Single‐Dose, Crossover Study in Healthy Adults

“…Inhaled glycopyrronium causes long-lasting bronchodilation in patients with COPD. 18 The major metabolic pathway of glycopyrronium involves hydroxylation of the cyclopentyl ring and oxidation of the hydroxyl group in the mandelic acid residue. 19 However, most (80%) of intravenously administered glycopyrronium is excreted unmetabolized in humans.…”

Inhaled Long-Acting Muscarinic Antagonists in Chronic Obstructive Pulmonary Disease

“…In the 1980s, the compound became of interest for the treatment of respiratory conditions when several pilot studies showed that inhaled glycopyrrolate (0.1-1.2 mg) displayed 8-12 h bronchodilatory activity in asthma and COPD patients [38][39][40]. The pharmacology of racemic glycopyrrolate was also characterized and compared with ipratropium bromide in guinea pig and human airways [41]. This evaluation showed that the compound displayed high affinity and no selectivity in its binding to the M 1 -M 3 receptors (K i values of 0.5-3.6 nM).…”