EFFECT OF PHENOBARBITAL AND SKF 525A PRETREATMENT ON DIPHENYLHYDANTOIN TERATOGENICITY IN MICE

¹ Oakdale Toxicology Center, Department of Pharmacology, College of Medicine, University of Iowa, Iowa City, Iowa

Diphenylhydantoin (DPH) treatment of primigravid Swiss-Webster mice is teratogenic and produces statistically significant increases in in utero deaths. Phenobarbital pretreatment significantly increases and 2-diethylaminoethyl- 2,2-diphenylvalerate hydrochloride (SKF 525A) pretreatment significantly decreases the plasma disappearance of DPH. These experiments indicate that phenobarbital probably stimulates and SKF 525A probably inhibits the metabolism of DPH in mice. Phenobarbital pretreatment significantly reduces and SKF 525A pretreatment significantly increases the incidence of DPH-induced fetal resorptions. Phenobarbital pretreatment does not antagonize the DPH-induced reduction of fetal body size, but SKF 525A pretreatment potentiates the response. Phenobarbital pretreatment antagonizes and SKF 525A pretreatment potentiates the DPH-induced orofacial and skeletal anomalies. These data indicate that under conditions which apparently stimulate DPH metabolism, diphenylhydantoin-induced teratogenicity is decreased; when conditions favor inhibition of DPH metabolism, teratogenicity is enhanced.

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