The clinical significance of food-induced changes in the absorption of theophylline from Uniphyl tablets

Abstract

To determine the effects of food on the absorption of theophylline from Uniphyl tablets (a once-daily sustained-release theophylline formulation), we performed a crossover evaluation in 20 adults with asthma. After 5 days of continuous dosing (at 6 pm), all patients received their regular Uniphyl dose under specified fasting conditions, and serum theophylline concentrations were measured sequentially during the following 24 hours. The patients' next Uniphyl dose was administered immediately after ingestion of a standardized high-fat meal, and theophylline concentrations were again measured during 24 hours. Five days later, the procedure was repeated in the opposite order. The patients' mean daily theophylline dose was 890.0 ± 229.2 mg. We found relatively minor, but in some cases statistically significant, differences in pharmacokinetic parameters between food and fasting administration. When Uniphyl was administered with food, bioavailability was increased by 10% ( p < 0.01), the time of maximum concentration occurred 3 hours later ( p < 0.01), and the minimum or “trough” theophylline concentration was 0.7 mg/L greater ( p < 0.01), as compared to administration while patients were fasting. There was no evidence of “dose dumping” after either food or fasting administration of Uniphyl, and there was no significant difference in the maximum theophylline concentration attained between the two dosing conditions. There was no evidence of a difference in therapeutic efficacy between the two dosing conditions. All patients tolerated the drug well throughout the trial.