Lack of effect of erythromycin on the pharmacokinetics of single oral doses of phenytoin

Abstract

The effect of erythromycin on the pharmacokinetics of phenytoin was studied in eight healthy volunteers using a balanced randomised cross-over design. Volunteers received a single oral dose of 400 mg of phenytoin sodium during each phase. During the treatment phase, the phenytoin sodium dose was administered 4.5 days after the commencement of a 7 day course of erythromycin base (250 mg every 6 h). There was no significant difference between the control and treatment phases (P greater than 0.05) with respect to the area under the plasma phenytoin concentration-time curve, the fraction of phenytoin unbound in plasma, the area under the unbound phenytoin concentration-time curve, the elimination half-life of phenytoin or the fraction of the dose excreted in urine as free and conjugated hydroxyphenylphenylhydantoin. This single dose study indicated that the intrinsic clearance of unbound phenytoin was unaffected by the concurrent administration of erythromycin.