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February 1971

Diphenylhydantoin Intoxication During Pregnancy: A Chemical Study of Drug Distribution in the Albino Rat

Author Affiliations

Charlottesville, Va
From the departments of neurology (Drs. Westmoreland and Bass) and pharmacology (Dr. Bass), University of Virginia School of Medicine, Charlottesville. Dr. Bass is a John and Mary R. Markle Scholar in Academic Medicine.

Arch Neurol. 1971;24(2):158-164. doi:10.1001/archneur.1971.00480320086008

DIPHENYLHYDANTOIN sodium is frequently given before and during the course of pregnancy to patients with convulsive disorders. It has been shown that most drugs are capable of crossing the placenta from mother to fetus, and that pharmacologic agents, relatively nontoxic to the adult, may have adverse effects on embryonic and fetal development.1 Diphenylhydantoin is a clinically toxic drug,2 and the chronic administration of large doses is said to cause irreversible damage to the central nervous system.3-6 Furthermore, the incidence of cleft palate is increased in the progeny of experimental animals receiving diphenylhydantoin.7,8 The present study was performed to assess the effects of diphenylhydantoin intoxication during pregnancy of the albino rat.

Materials and Methods 

Production of Diphenylhydantoin Intoxication.—  Seventy-five Charles River CD strain adult albino rats weighing 250 to 300 gm were used. Fourteen pregnant rats at 14 days of gestation and 61 nonpregnant rats were

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