Phenobarbital does not alter phenytoin steady-state serum concentration or pharmacokinetics.

Phenytoin pharmacokinetics and biotransformation were studied with stable isotope tracer techniques in six patients before and after addition of phenobarbital. No significant (p less than 0.05) changes in phenytoin serum concentration, clearance, elimination half-life, volume of distribution, or clearance via production of p-hydroxyphenyl-phenylhydantoin or phenytoin dihydrodiol occurred after addition of phenobarbital. Thus, frequent phenytoin serum concentration determinations or a change in phenytoin dosing rate are probably not necessary after adding phenobarbital.