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J Allergy Clin Immunol. 1986 Oct;78(4 Pt 2):736-42.

Therapeutic consequences of drug interactions with theophylline pharmacokinetics.


Elimination of theophylline from the body occurs mainly (approximately 90%) by biotransformation, followed by excretion of the metabolites. Consequently, drugs affecting microsomal enzyme systems in the liver may alter the elimination of theophylline. Since theophylline has a rather narrow therapeutic window, dose adjustment might be necessary. Of the sympathomimetics, isoproterenol reduces theophylline clearance by 25%, but metaproterenol and terbutaline do not. Of the antibiotics, erythromycin and troleandomycin decrease theophylline clearance by 25% and 50%, respectively. No effect was observed with tetracycline, doxycycline, amoxicillin, cefaclor, and co-trimoxazole. On the other hand, rifampin (antituberculotic agent) increases theophylline clearance by 30%. Corticosteroids (hydrocortisone, methylprednisolone, and prednisone) do not affect theophylline kinetics. Influenza vaccination also has no influence. The antiulcerative agent (H2 antagonist) cimetidine decreases theophylline clearance by 30%, but the agent ranitidine does not have any effect. Oral contraceptives may decrease theophylline elimination by 30%. Barbiturates and phenytoin may enhance theophylline clearance substantially (up to 75%). If an interaction is expected, careful monitoring of theophylline plasma concentrations is required to optimize the dose.

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