Phenobarbital does not alter phenytoin steady‐state serum concentration or pharmacokinetics

Abstract

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.

Phenobarbital population pharmacokinetics across the pediatric age spectrum

“…The small sample of interacting medication should be considered when interpreting the clinical outcomes potentially associated with these outcomes. The interaction between phenobarbital and phenytoin (enteral) is controversial, with some reports identifying an interaction that increases phenobarbital serum concentrations, others identifying increased phenytoin concentrations, and others with no interaction at all . An investigation by Encinas et al demonstrated that phenobarbital serum concentrations were initially elevated with concomitant phenytoin administration, but normalized over time .…”

“…The interaction between phenobarbital and phenytoin (enteral) is controversial, with some reports identifying an interaction that increases phenobarbital serum concentrations, others identifying increased phenytoin concentrations, and others with no interaction at all. [26][27][28][29] An investigation by Encinas et al demonstrated that phenobarbital serum concentrations were initially elevated with concomitant phenytoin administration, but normalized over time. 28 The data presented 30 The concomitant use of pantoprazole with phenobarbital in this analysis demonstrated increased CL of phenobarbital, suggesting induction of metabolism.…”

Intestinal expression of cytochrome P450 enzymes and ABC transporters and carbamazepine and phenytoin disposition

“…However, for ethical reasons it was not possible to discontinue phenobarbital comedication in these four patients. As carbamazepine and phenytoin are among the most potent inducers of hepatic metabolism, the effect of phenobarbital on the metabolism of these two drugs is expected to be low (28) or even absent (29).…”