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AIMS: We investigated whether the deterioration in asthma control reported following cessation of theophylline was due to tolerance to theophylline. METHODS: Eighteen subjects with mild stable asthma were given oral theophylline 10 mg kg(-1) day(-1) or placebo for 2 weeks in a double-blind crossover study. FEV1 and PD20 histamine were measured before and 8 h after the first dose of treatment and 8, 32 and 56 h after the final dose. PD20 AMP was measured before treatment and 9 h after the final dose. RESULTS: Six patients did not tolerate theophylline. In the other 12 subjects there were no differences between treatments in daily PEF, symptom scores, rescue bronchodilator use, PD20 histamine or FEV1 up to 8 h post treatment. Following withdrawal of theophylline there were significantly lower values for mean FEV1 (mean difference 0.151, 95% CI 0.03, 026) and PD20 AMP compared to placebo but no difference in other end points. CONCLUSIONS: The small rebound deterioration in lung function following regular treatment with therapeutic doses of oral theophylline is consistent with the development of tolerance.

Type

Journal article

Journal

Br J Clin Pharmacol

Publication Date

04/1998

Volume

45

Pages

402 - 404

Keywords

Administration, Oral, Adult, Asthma, Bronchoconstriction, Bronchodilator Agents, Cyclic AMP, Double-Blind Method, Female, Forced Expiratory Volume, Histamine, Humans, Male, Middle Aged, Placebos, Substance Withdrawal Syndrome, Theophylline