Effects of Oral Theophylline Combined with Oral and Inhaled β2-Adrenostimulants in Asthmatics

The acute ventilatory, cardiovascular and tremorogenic effect of a high oral dose of terbutaline (5 mg) was compared with that of half the dose (2.5 mg) combined with 280 mg anhydrous theophylline orally in the randomized, double-blind, cross-over study in eight asthmatics. After 120 min, when steady-state bronchodilation was achieved, five terbutaline inhalations (1.25 mg terbutaline sulphate) were added to both treatment regimens. The mean maximum plasma concentration of theophylline was then 7 micrograms/ml (39 mumol/l). Inhalation of a beta 2-adrenostimulant had a very good additional effect without increasing side effects in these patients with good inhalation technique. The oral low-dose combination gave significantly better bronchodilation than the high dose of terbutaline alone and caused significantly less tremor. Although the combination only had an additive bronchodilating effect, it may offer important clinical advantages. If the patient cannot use the metered dose aerosol, an oral low dose combination should be preferred to a single high dose of either theophylline or beta 2-adrenostimulants. In patients with good inhalation technique but not controlled by inhalation from a metered dose aerosol alone, a combination of oral theophylline and terbutaline in "sub-optimal" dose and an inhaled beta 2-agonist in individually titrated optimal dose gave a maximal bronchodilating effect with minimum side effects.