Abstract:
PURPOSE:This study was designed to measure the brain penetration of phenytoin (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 measured in serum, protein-free ultrafiltrate, and in brain, by using high-performance liquid chromatography. RESULTS:Although the initial PHT-free fraction was significantly higher for 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 epilepticus, it should be anticipated that lower initial brain PHT levels will be achieved than are typically found with standard PHT.
journal_name
Epilepsiajournal_title
Epilepsiaauthors
Walton NY,Uthman BM,El Yafi K,Kim JM,Treiman DMdoi
10.1111/j.1528-1157.1999.tb02068.xsubject
Has Abstractpub_date
1999-02-01 00:00:00pages
153-6issue
2eissn
0013-9580issn
1528-1167journal_volume
40pub_type
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