EVALUATION OF PHARMACOKINETIC INTERACTION BETWEEN BROMFENAC AND PHENYTOIN IN HEALTHY-MALES

An open-label, nonrandomized, multiple-dose, inpatient study was condu cted in healthy male volunteers to compare the pharmacokinetics of bro mfenac and phenytoin when the drugs are given individually and concomi tantly. Twelve men received multiple oral doses of bromfenac for 4 day s and then oral phenytoin for up to 14 days followed by concomitant ad ministration of bromfenac and phenytoin for 8 days. Concomitant admini stration of the two drugs caused an approximate 40% decrease in the me an peak plasma concentration (C-max) and the interdose area under the concentration-time curve (AUG) of bromfenac. The oral clearance (Cl-po ) of bromfenac doubled and the volume of distribution increased by 77% . For phenytoin, the mean peak serum concentration and the AUC increas ed by 9% and 11%, respectively, in the presence of bromfenac. The only change in unbound phenytoin was a 16% increase in the AUC. Although s tatistically significant, the changes in the pharmacokinetic parameter s of phenytoin and unbound phenytoin were small. Adjustments in the do se of phenytoin should not be required during concomitant administrati on of bromfenac, although each patient's clinical status should be eva luated individually.