Effect of (dl) 3,7-dihydro-1,8-dimethyl-3-(2-methylbutyl)-1H-purine-2,6-dione on exercise-induced bronchospasm.

The authors studied the clinical activity of a synthetic theophylline derivative, (dl)-dihydro-1,8-dimethyl-1-3-(-2-methyl-butyl)-1 H-purine-2,6 dione, both after short-term treatment and in prevention of Exercise-Induced Asthma (EIA). The action of the new compound at two dosages was compared with that of anhydrous theophylline at a standard dose of 600 mg/day. The trial included 15 asthmatics, 11 males and 4 females, who showed EIA with reversible bronchospasm (improvement of at least 15% of FEV1 after administration of salbutamol at a dose of 200 mcg by means of a predosed aerosol). Asthma had been provoked by free running on a flat surface. The test was considered positive if the FEV1 was reduced at least by 20% compared with baseline level. Only 11 patients completed the protocol. In four cases the treatment had to be withdrawn due to the onset of adverse side effects. After 3 days of treatment, the drug caused a statistically significant improvement of FEV1 in comparison with baseline, but no difference from that caused by theophylline. Likewise no significant difference was noted between low and high doses of the tested drug. As regards the behavior of EIA under treatment, in 8 of 14 patients theophylline and the investigational drug proved equally effective. Two patients were protected only by theophylline, one only by the investigational drug, and three failed to be protected by either agent. The higher dose of the investigational drug protected against EIA in all the subjects protected by theophylline with one exception. Of the two doses tested, the lower one should be preferred since it has the same therapeutic effect without the most important side effects.