Interaction between phenytoin and theophylline in healthy volunteers

1. The effect of phenytoin, 100 mg thrice daily for 3 weeks, on theophylline disposition was studied in eight healthy volunteers. 2. The anticonvulsant significantly reduced the half-life of theophylline and this was associated with an increase in the rate of theophylline clearance. The volume of distribution was not significantly altered. 3. There was no correlation between initial theophylline clearance and its percentage increase after phenytoin pretreatment. 4. Coefficients of variation in theophylline clearance before and after phenytoin pretreatment were similar. 5. It is suggested that phenytoin induces theophylline metabolism, that initial theophylline metabolism is not a determinant of the extent of such induction, and that there is a similar potential for induction among healthy volunteers.