Therapeutic effect and dosing strategies for theophylline in the treatment of chronic asthma

Theophylline has demonstrated a very high degree of clinical efficacy as a prophylactic maintenance drug for chronic asthma when dose levels maintain serum concentrations of 10 to 20 micrograms/ml. Once established, such doses appear to be well tolerated and free of clinically apparent side effects, although minor neuropsychological and physiologic abnormalities can be detected. In general, while there appears to be little clinical effect from these minor side effects, the possibility of bothersome symptoms in selected patients cannot be excluded and requires further study. The data argue strongly that formulations and dosage intervals should aim for the most stable serum concentrations practically attainable, even though clinicians will certainly make justifiable compromises in individual clinical situations. The wide variability in theophylline elimination rate and the relationship between effect and serum concentration dictate that dosage be individualized and that final dosage is best guided by measurement of serum concentration. Slow clinical titration decreases the frequency of caffeine-like side effects from greater than 50% of patients when therapeutic levels are rapidly attained to only 1% or 2%. Finally, although some physiologic variables and drug interactions may alter theophylline elimination and thus pose clinical risks, it is reassuring that dosage requirements generally remain stable over extended periods.