The effects of theophylline on serum alprazolam levels

Theophylline and benzodiazepines are frequently combined in clinical practice. Because of a number of case reports about antagonism of benzodiazepine-induced sedation by theophylline, we investigated serum alprazolam levels in a convenient sample of pulmonary medicine inpatients receiving theophylline and no theophylline. One mg of alprazolam was given daily for seven days to 6 patients receiving theophylline and 7 patients not receiving theophylline treatment. On days 2 through 7, trough serum alprazolam levels were measured. On day 7, blood samples were collected before (0 hour), and at 3, 6, 9 and 12 hours after alprazolam administration. In patients receiving theophylline, serum trough alprazolam levels were significantly lower during each day of the study. In patients receiving no theophylline, serum alprazolam levels were in the therapeutic range, except for two patients who had high alprazolam levels. In this small study, serum alprazolam levels were found to be consistently below the therapeutic range in patients receiving chronic theophylline treatment. Previously reported antagonism of anxiolytic effects of benzodiazepines by theophylline is probably due to the lower serum benzodiazepine levels in these patients.