Predisposition to phenytoin hepatotoxicity assessed in vitro

S. P. Spielberg, G. B. Gordon, D. A. Blake, D. A. Goldstein, H. F. Herlong

Research output: Contribution to journalArticle

Abstract

Arene oxide metabolites of phenytoin may be involved in the pathogenesis of drug-induced hepatotoxicity. We examined individual susceptibility to toxicity from such metabolites by exposing human lymphocytes to metabolites generated by a murine hepatic microsomal system. Cells from 17 controls showed no toxicity at concentrations of phenytoin from 31 to 125 μM. Cells from three patients with phenytoin hepatotoxicity manifested dose-dependent toxicity from the metabolites. Phenytoin alone was not toxic to cells. The patients' dose-response curves resembled the response of control cells in which epoxide hydrolase (a detoxification of non-arene oxide metabolites (e.g., of acetaminophen) was normal in patients' cells. Cells from parents of two patients had intermediate responses. Cells from a sibling of one patient showed no toxicity; a sibling of another patient had a response similar to that of the patient. A heritable defect in response to arene oxides thus may predispose some patients to phenytoin hepatotoxicity.

Original languageEnglish (US)
Pages (from-to)722-727
Number of pages6
JournalNew England Journal of Medicine
Volume305
Issue number13
StatePublished - 1981
Externally publishedYes

Fingerprint

Phenytoin
Oxides
Siblings
Epoxide Hydrolases
In Vitro Techniques
Poisons
Acetaminophen
Parents
Lymphocytes
Liver
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Spielberg, S. P., Gordon, G. B., Blake, D. A., Goldstein, D. A., & Herlong, H. F. (1981). Predisposition to phenytoin hepatotoxicity assessed in vitro. New England Journal of Medicine, 305(13), 722-727.

Predisposition to phenytoin hepatotoxicity assessed in vitro. / Spielberg, S. P.; Gordon, G. B.; Blake, D. A.; Goldstein, D. A.; Herlong, H. F.

In: New England Journal of Medicine, Vol. 305, No. 13, 1981, p. 722-727.

Research output: Contribution to journalArticle

Spielberg, SP, Gordon, GB, Blake, DA, Goldstein, DA & Herlong, HF 1981, 'Predisposition to phenytoin hepatotoxicity assessed in vitro', New England Journal of Medicine, vol. 305, no. 13, pp. 722-727.
Spielberg SP, Gordon GB, Blake DA, Goldstein DA, Herlong HF. Predisposition to phenytoin hepatotoxicity assessed in vitro. New England Journal of Medicine. 1981;305(13):722-727.
Spielberg, S. P. ; Gordon, G. B. ; Blake, D. A. ; Goldstein, D. A. ; Herlong, H. F. / Predisposition to phenytoin hepatotoxicity assessed in vitro. In: New England Journal of Medicine. 1981 ; Vol. 305, No. 13. pp. 722-727.
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