Phenytoin impairs the bioavailability of dexamethasone in neurological and neurosurgical patients.

Plasma concentration-time data after oral and intravenous administration of dexamethasone have been subjected to pharmacokinetic analysis in six neurological or neurosurgical patients taking the steroid with phenytoin, and in nine patients (one studied twice) taking dexamethasone without phenytoin. An additional patient was studied before and during phenytoin intake. Apparent volume of distribution was similar in the two groups, but the group treated with phenytoin had an almost statistically significantly shorter dexamethasone mean terminal half-life, an approximately trebled mean plasma clearance, and a mean oral bioavailability of the steroid of only 33%, compared with a mean 84% oral bioavailability in those not receiving phenytoin. To achieve a given plasma dexamethasone concentration, patients treated with the steroid and phenytoin may need oral dexamethasone doses several times those required by patients not receiving phenytoin.