Walton N Y, Uthman B M, El Yafi K, Kim J M, Treiman D M
Research and Neurology Services, VA Medical Center, West Los Angeles, California, USA.
Epilepsia. 1999 Feb;40(2):153-6. doi: 10.1111/j.1528-1157.1999.tb02068.x.
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.
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.
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.
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.
本研究旨在测量静脉注射标准苯妥英（PHT）或磷苯妥英（FPHT，一种PHT前体药物）后苯妥英在脑内的渗透情况。该研究旨在回答FPHT在血液中转化为PHT所需的时间是否会延迟PHT在脑内的蓄积这一问题。
对4只大鼠静脉输注30mg/kg PHT或30mg/kg PHT当量的FPHT后，在不同时间点进行采样。采用高效液相色谱法测定血清、无蛋白超滤液和脑内的PHT含量。
尽管FPHT处理组大鼠最初的游离PHT分数显著高于PHT处理组大鼠，但输注FPHT后脑内PHT水平显著降低。
当使用FPHT治疗全身性癫痫持续状态时，应预期与标准PHT相比，最初脑内PHT水平会更低。
