The effect on the
allergen-induced immediate and late bronchoconstriction of
theophylline and
enprofylline (3-propylxanthine), a new
xanthine derivative with negligible ability to antagonize
adenosine, was studied in nine patients with
asthma. The patients were challenged three times at weekly intervals with the same dose of
allergen. FEV1 and SGaw were followed up to 6 hours after challenge. The drugs were administered intravenously. Placebo was always administered on the first occasion.
Theophylline and
enprofylline were administered on test days 2 and 3 with a double-blind, randomized crossover technique. One hour before the
allergen challenge, a loading dose was administered during 60 minutes followed by a constant infusion during 6 hours. The loading infusion was 7.2 mg/kg of
theophylline and 2.7 mg/kg of
enprofylline. The maintenance dose was 74 mg/hr and 71 mg/hr, respectively. Both
theophylline and
enprofylline caused a minor initial bronchodilatation.
Theophylline and
enprofylline slightly but significantly attenuated the immediate bronchoconstricting reaction after
allergen inhalation.
Theophylline and
enprofylline had a significant attenuating effect on the late bronchial reaction. The mean plasma level of
theophylline was 0, 10.8, 10.5, and 10.5 mg/L at 0, 1, 4, and 7 hours after the start of the loading infusion, respectively. The corresponding mean plasma levels of
enprofylline were 0, 2.6, 2.7, and 2.7 mg/L.
Theophylline and
enprofylline caused
headache in one patient. Two patients developed
nausea and
vomiting during the
enprofylline infusion. The present data suggest that
adenosine receptor antagonism may not be the main mode of action of
xanthines in inhibiting bronchoconstriction after single dose
antigen challenge.