Phenytoin-oxacillin interactions in normal and uremic sera

Area of Science:

• Pharmacology
• Drug Interactions
• Clinical Pharmacy

Background:

• Phenytoin is highly protein-bound, with 90% bound to albumin.
• Displacement by other albumin-bound drugs can increase free phenytoin concentrations.
• Oxacillin, an antibiotic, is also strongly albumin-bound and often co-administered with phenytoin.

Purpose of the Study:

• To investigate the potential displacement of phenytoin by oxacillin.
• To evaluate the impact of oxacillin concentration on free phenytoin levels.
• To assess this interaction in specific patient populations like those with hypoalbuminemia or uremia.

Main Methods:

• Serum pools from phenytoin patients, uremic patients, and hypoalbuminemic patients were prepared.
• Phenytoin and varying concentrations of oxacillin (15 and 50 µg/ml) were added.
• Free phenytoin concentrations were measured.
• A case study in a hypoalbuminemic patient receiving high-dose intravenous oxacillin was monitored.

Main Results:

• Oxacillin at 50 µg/ml significantly increased free phenytoin concentration in a general patient serum pool.
• Both 15 and 50 µg/ml oxacillin concentrations significantly increased free phenytoin in uremic and hypoalbuminemic serum pools.
• In vivo monitoring showed increasing free phenytoin fraction with escalating oxacillin therapy in one patient.

Conclusions:

• The phenytoin-oxacillin interaction is generally not significant at lower oxacillin doses used in oral therapy.
• High concentrations of oxacillin, especially in patients with hypoalbuminemia or uremia, may lead to clinically significant displacement of phenytoin.
• Careful monitoring is advised when high-dose oxacillin is administered to patients on phenytoin therapy.