Treatment of epilepsy with diphenylhydantoin (5,5-diphenylhydantoin, phenytoin, Dilantin) or phenobarbital (5-ethyl-5-phenylbarbituric acid) aims at the maintenance of constant and therapeutically effective concentrations of the drugs in the central nervous system. A rational drug regimen requires knowledge as to the serum level requisite for anticonvulsant effect, the relationship between the serum level and the dosage given, and the rate of accumulation. There is evidence that the concentration of both drugs in human serum is equal, or proportional, to that in brain. In rats, rabbits, and dogs diphenylhydantoin and phenobarbital are distributed about equally in serum and brain,2-4 and a few determinations of phenobarbital post mortem indicate that the same is true in man.5 Similarly, a single dose of phenobarbital applied intramuscularly to the mother resulted in identical concentrations in fetal serum and cerebral cortex, whereas concentrations more than twice as high occurred in the region of the fourth ventricle.
SVENSMARK O, BUCHTHAL F. Diphenylhydantoin And PhenobarbitalSerum Levels in Children. Am J Dis Child. 1964;108(1):82–87. doi:10.1001/archpedi.1964.02090010084011
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