Phenytoin penetration into brain after administration of phenytoin or fosphenytoin

Purpose: This study was designed to measure the brain penetration of phenyt oin (PHT) after intravenous (i.v.) administration of either standard PHT or fosphenytoin (FPHT), a PHT prodrug. The study was formulated to answer the question whether the time required for FPHT to be converted to PHT in the bloodstream would delay the accumulation of PHT in brain. Methods: Four rats were sampled at Various times after intravenous infusion of 30 mg/kg PHT i.v. or 30 mg/kg PHT equivalents of FPHT i.v. PHT was meas ured in serum, protein-free ultrafiltrate, and in brain, by using high-perf ormance liquid chromatography. Results: Although the initial PHT-free fraction was significantly higher fo r FPHT-treated rats than it was for PHT-treated rats, brain PHT levels were significantly reduced after infusion of FPHT. Conclusions: When FPHT is used for treatment of generalized status epilepti cus, it should be anticipated that lower initial brain PHT levels will be a chieved than are typically found with standard PHT.