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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Methylxanthines inhibit exercise-induced bronchoconstriction at low serum theophylline concentration and in a dose-dependent fashion.

We studied the relationship between attenuation of exercise-induced bronchoconstriction and serum theophylline concentration in a dose-dependent fashion in 11 patients with mild bronchial asthma. In addition, we investigated the protection of equal amounts of theophylline either dissolved in ethylenediamine or in proxyphylline and diprophylline. At 4 separate study days, the patients received one of the following preparations in a double-blind random order: saline solution, 200 mg of theophylline in 19.9 mg of ethylenediamine (TE200), 351 mg of theophylline in 35 mg of ethylenediamine (TE351), and 200 mg of theophylline in 300 mg of propxyphylline and 300 mg of diprophylline (TPD). Fifteen minutes after the end of infusion, a standardized exercise test during cold air breathing was performed. Before and up to 30 minutes after each test, specific airway resistance and FEV, were determined. Postexertional bronchoconstriction after theophylline was expressed by means of a protection index, a value of 0 or 1 meaning no or full protection, respectively. At mean (SD) serum theophylline concentrations of 6.7 (1.3), 10.1 (1.7), and 6.3 (1.4) mg/L, respectively, TE200, TE351, and TPD for specific airway resistance caused a significant bronchodilation (p less than 0.05) and resulted in mean (SD) protection indices of 0.61 (0.15), 0.82 (0.14), and 0.65 (0.20), respectively, being significantly different from 0 (p less than 0.01). The protective effect of TE200 and TPD was equal and significantly less pronounced as compared to TE351 (p less than 0.01). Therefore, theophylline attenuated exercise-induced bronchoconstriction in a dose-dependent fashion with significant protection at serum concentrations of about 6 mg/L. The effect of intravenous theophylline was independent of the diluents.[1]


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