Displacement of phenytoin from serum protein carriers by antibiotics: studies with ceftriaxone, nafcillin, and sulfamethoxazole

Abstract

Abstract Increased concentrations of free phenytoin in serum, attributable to the displacement of this anticonvulsant by other drugs, e.g., valproic acid and salicylic acid, have been reported. We observed in vitro and in vivo displacement of phenytoin by the antibiotics ceftriaxone, nafcillin, and sulfamethoxazole. In vitro studies demonstrated statistically significant (P less than 0.05) increases in free phenytoin after the addition of specific antibiotics to patients' sera and to phenytoin-supplemented sera from controls. Concentrations of free phenytoin in vivo, predicted by an equation we have found to be accurate for albumin concentrations greater than or equal to 32 g/L, were consistently underestimated in patients receiving concomitant therapy with the antibiotics studied. The concentrations of free phenytoin decreased towards the predicted values when the antibiotic therapy was discontinued. We conclude that ceftriaxone, nafcillin, and sulfamethoxazole can displace phenytoin from the usual protein carriers found in serum, in vitro and in vivo.