Slow-release oral salbutamol and aminophylline in nocturnal asthma: relation of overnight changes in lung function and plasma drug levels.

Abstract

In a double-blind controlled trial 14 chronic asthmatic patients with regular nocturnal exacerbations took 16 mg slow-release oral salbutamol (two Ventolin spandets), 450 mg slow-release aminophylline (two Phyllocontin Continus tablets), or placebo at midnight. Mean peak expiratory flow rates on waking were significantly higher on the active drugs than on placebo (p<001 for salbutamol; p < 005 for aminophylline) but neither drug abolished the overnight fall in PEFR. Plasma drug levels at 0600 hr were 17-3 ng/ml (+5 3 ng/ml SD) for salbutamol, and 7-1 ig/ml (±3 1 ig/ml SD) for theophylline. Steady-state data derived from plasma levels of salbutamol during intravenous infusion indicated that the morning salbutamol levels were probably in a therapeutic range for asthma. The morning theophylline levels, however, were suboptimal when aminophylline was given only at night.Early morning wheezing is a common symptom of asthma for which sustained release bronchodilator tablets are frequently prescribed. In normal people a diurnal variation of peak expiratory flow (PEFR) of up to 10% has been obs,erved.1 However, in asthma much larger variations frequently occur, and may sometimes pass unnoticed by the patient.2 These overnight falls in PEFR may continue apparently harmlessly foTr many years or may be associated with deterioration in the overall control of the subject's asthma.3 4Although slow-release bronchodi-lator preparations are widely prescribed to prevent nocturnal symptoms of asthma, there are few data to suggest the correct dose based on measurement of drug plasma levels. Information is available on the therapeutically effective range of plasma levels of theophylline for acute and chronic asthma, but there is no such information for salibuta,mol. This study was undertaken to investigate the plasma levels of salbutamol and theophylline produced by slow-release oral preparations, and to relate these to the degree of control achieved in chronic nocturnal asthma and

Drug Intake and Plasma Concentrations in Acute Asthma

“…Concerning /2-agonists, plasma concentrations after oral intake [4,12], subcutaneous injection [24], nebulized so lution [25], and metered aerosol [19, 23] were studied and therapeutic ranges dis cussed.…”

Protective effect of theophylline on histamine‐induced bronchoconstriction in asthmatic children.

“…Airway calibre decreases in the early hours of the morning and it has been suggested that the exaggerated fall in airway calibre in the asthmatic at this time is a manifestation of increased bronchial responsiveness (Barnes, 1984). Both theophylline and jadrenoceptor agonists given orally have been recommended for the management of nocturnal asthma and both result in improved PEFR measurements on waking in the morning (Fairfax et al, 1980). Oral ,3-adrenoceptor agonists, however, have little effect on bronchial responsiveness (Cockroft et al, 1977a) and our present study has shown that the effect of theophylline is similarly small.…”

Comparison of a Combination of Fenoterol with Ipratropium Bromide (Duovent) and Salbutamol in Young Adults with Nocturnal Asthma

“…Regular treatment with inhaled pj-agonists and corticosteroids is helpful [7]. Slow-release oral preparations of |T-agonists are not effective [6] and although slow-release preparations of theophylline can be useful [3], they may be difficult to use in practice because of the narrow plasma therapeutic range. As a conse quence of their different modes of action the combination of a (32-agonist with an anticholinergic drug may produce a grea ter bronchodilator response than that which can be achieved when either agent is used alone.…”