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Massive Theophylline Dosing in a Heavy Smoker Receiving Both Phenytoin and Phenobarbital

OBJECTIVE: To report unusually high theophylline dosing requirements in a smoker receiving concomitant therapy with phenytoin and phenobarbital. DESIGN: Single case report. SETTING: 517-bed, university teaching hospital. PATIENT: 29-year-old woman with newly diagnosed asthma, heavy smoking history, and a seizure disorder. RESULTS: The additive influence of smoking, phenytoin, and phenobarbital greatly increased the theophylline dosing requirements. Doses of up to 4 g/d (59 mg/kg/d) were required to achieve adequate symptomatic relief of her asthma as well as to provide therapeutic serum theophylline concentrations. CONCLUSIONS: Multiple polymorphisms may additively influence theophylline metabolism and exceptionally large theophylline doses may be required in some patients who smoke and are comedicated with phenytoin and phenobarbital.