Clinical and experimental studies linking oxidative metabolism to phenytoin-induced teratogenesis

R. H. Finnell, B. A. Buehler, B. M. Kerr, P. L. Ager, R. H. Levy

Research output: Contribution to journalArticle

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Abstract

Article abstract-The research presented in this article concerns the proposed mechanism of phenytoin-induced teratogenicity that focuses on oxidative metabolites as sources of reactive species in clinical studies and by testing paradigms in animal models. The clinical aspect involved determining whether at-risk fetuses could be detected prenatally on the basis of low or deficient epoxide hydrolase activity. In 19 pregnancies monitored by amniocentesis, we predicted an adverse outcome in four infants on the basis of low enzyme activity. When examined neonatally, all four infants had the dysmorphic features of the “fetal hydantoin syndrome.” In an animal model of phenytoin-induced ter- atogenesis, the level of fetal exposure to oxidative metabolites was decreased by coadministration of the cytochrome P- 450-inhibiting antiepileptic drug stiripentol, which significantly reduced the incidence of phenytoin-induced congenital malformations in two of the three inbred mouse strains, thus providing support for the hypothesis that oxidative metabolites are critical in mediating phenytoin teratogenesis.

Original languageEnglish (US)
Pages (from-to)25-31
Number of pages7
JournalNeurology
Volume42
Issue number4
StatePublished - Apr 1992

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Teratogenesis
Phenytoin
Animal Models
Epoxide Hydrolases
Inbred Strains Mice
Amniocentesis
Anticonvulsants
Cytochrome P-450 Enzyme System
Fetus
Pregnancy
Clinical Studies
Incidence
Enzymes
Research

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Finnell, R. H., Buehler, B. A., Kerr, B. M., Ager, P. L., & Levy, R. H. (1992). Clinical and experimental studies linking oxidative metabolism to phenytoin-induced teratogenesis. Neurology, 42(4), 25-31.

Clinical and experimental studies linking oxidative metabolism to phenytoin-induced teratogenesis. / Finnell, R. H.; Buehler, B. A.; Kerr, B. M.; Ager, P. L.; Levy, R. H.

In: Neurology, Vol. 42, No. 4, 04.1992, p. 25-31.

Research output: Contribution to journalArticle

Finnell, RH, Buehler, BA, Kerr, BM, Ager, PL & Levy, RH 1992, 'Clinical and experimental studies linking oxidative metabolism to phenytoin-induced teratogenesis', Neurology, vol. 42, no. 4, pp. 25-31.
Finnell RH, Buehler BA, Kerr BM, Ager PL, Levy RH. Clinical and experimental studies linking oxidative metabolism to phenytoin-induced teratogenesis. Neurology. 1992 Apr;42(4):25-31.
Finnell, R. H. ; Buehler, B. A. ; Kerr, B. M. ; Ager, P. L. ; Levy, R. H. / Clinical and experimental studies linking oxidative metabolism to phenytoin-induced teratogenesis. In: Neurology. 1992 ; Vol. 42, No. 4. pp. 25-31.
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