Phenytoin-Oxacillin Interactions in Normal and Uremic Sera

Displacement of phenytoin (90% bound to albumin) by other strongly albumin-bound drugs such as salicylate and valproic acid may result in an increase in pharmacologically active free concentrations. The antibiotic oxacillin is also strongly bound to albumin and is often administered to patients receiving phenytoin. Oxacillin at a concentration of 15 μg/ml caused no significant displacement of phenytoin in a serum pool prepared from patients receiving phenytoin. However, a significant increase in the free phenytoin concentration was seen at an oxacillin concentration of 50 μg/ml. We also prepared a serum pool from uremic patients and another from patients with hypoalbuminemia and supplemented both of them with phenytoin. Significant increases in the free phenytoin concentration occurred with both 15- and 50-μg/ml concentrations of oxacillin. In one hypoalbuminemic patient receiving both phenytoin and intravenous high-dose oxacillin, the free phenytoin fraction was 22.5% before oxacillin therapy, 24.1% 12 hours after first dose of oxacillin, and 27.2% after 60 hours, indicating the possibility of in vivo displacement of phenytoin by oxacillin. We conclude that the phenytoin-oxacillin interaction is not significant at lower dosages of oxacillin usually prescribed for oral therapy. However, the interaction may be significant at high concentrations of oxacillin, especially in patients with hypoalbuminemia or uremia.