Nafcillin is a semisynthetic penicillin analogue that remains in clinical use because of its activity against penicillinase-producing Staphylococcus aureus. It is absorbed in the intestine and is primarily eliminated via hepatic metabolism . Less than 30% of administered nafcillin is excreted renally, with approximately 8% eliminated in the bile .
In a study by Veremis et al., it was reported that nafcillin decreased the concentration of the immunosuppressive agent, cyclosporin. The activity of CYP3A enzyme is critical to the biotransformation of cyclosporin and is the rate-limiting step in the elimination of cyclosprorine . In another case study by Qureshi et al., it was found that nafcillin enhanced warfarin elimination. The interaction did not appear to be related to warfarin's absorption and extent of protein binding but rather to apparent hepatic microsomal enzyme induction. These findings suggest that nafcillin may be an inducer of CYP activity. In this study, we have tested this hypothesis by investigating the effect of nafcillin pretreatment on the pharmacokinetic parameters of nifedipine, an index substrate of CYP3A in humans.