Separate and combined use of terbutaline and theophylline in asthmatics. Effects related to plasma levels

Abstract

The bronchodilating properties and side effects of theophylline and a beta 2-adrenoceptor stimulating drug (terbutaline) alone and in combination were studied in 10 adult asthmatic patients. Initially, each individual's pharmacokinetic parameters for theophylline were determined. On 3 separate days theophylline was infused to defined steady-state concentrations (0, 7.5, and 15 microgram/ml, respectively) followed by the administration, at 1-h intervals, of incremental i.v. doses of terbutaline. It was shown that: 1. Theophylline caused a concentration-dependent increase in FEV1. Theophylline itself had no significant effect on objectively recorded skeletal muscle tremor or heart rate but enhanced the terbutaline-induced increase in tremor and heart rate. At the highest concentration (15 microgram/ml) two of the patients experienced nausea. 2. Terbutaline caused a concentration-dependent increase in FEV1, heart rate, and tremor. The plasma levels of terbutaline at the given doses did not differ significantly between individuals or within individuals at the different theophylline levels. 3. The combination of theophylline and terbutaline resulted in a mere additive effect on the bronchodilatation. At comparable bronchodilatation the combination of theophylline and terbutaline caused a lesser degree of side effects than each of the drugs alone.