Evaluation of serum levels during prolonged combination therapy with phenytoin and phenobarbitone

When phenobarbitone was added to the treatment regimen of epileptic patients who received phenytoin only, the serum levels of phenytoin increased significantly within 6 weeks. Eleven weeks after the introduction of phenobarbitone, phenytoin levels had returned to those existing before phenobarbitone therapy. In view of possible complex pharmacokinetic interactions which might occur when phenobarbitone is added to a regimen of phenytoin, or vice versa, frequent measurement of serum drug levels appears to be indicated for up to 10 weeks after effecting a change in treatment. During this period a constant change in serum levels could be expected, resulting either in toxicity or lack of efficacy.