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. 1977 Sep;40(9):890–895. doi: 10.1136/jnnp.40.9.890

Phenytoin intoxication during concurrent diazepam therapy

Howard J Rogers 1,2,1, Robert A Haslam 1,2, James Longstreth 1,2, Paul S Lietman 1,2
PMCID: PMC492863  PMID: 599366

Abstract

Phenytoin elimination is a saturable process obeying Michaelis-Menten kinetics. Plasma phenytoin levels are not related linearly to dose, and small changes in enzyme activity produced by concurrent drug therapy could alter plasma levels. Two cases of phenytoin intoxication associated with simultaneous administration of diazepam are reported. Intravenous phenytoin infusions were given and the apparent Km and Vmax computed from the resulting plasma phenytoin levels. In one case `Km' and `Vmax' were 0.8 μmol/1 and 1.3 μmol/1/hour respectively during concurrent diazepam administration, and 50.3 μmol/1 and 4.4 μmol/1/hour after discontinuation of diazepam. In the second case phenytoin infusion with diazepam gave `Km' and `Vmax' values of 0.012 μmol/1 and 0.95 μmol/1/hour. Without diazepam these were 28.8 μmol/1 and 0.92 μmol/1/hour respectively.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bochner F., Hooper W. D., Tyrer J. H., Eadie M. J. Effect of dosage increments on blood phenytoin concentrations. J Neurol Neurosurg Psychiatry. 1972 Dec;35(6):873–876. doi: 10.1136/jnnp.35.6.873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Dawson K. P., Jamieson A. Value of blood phenytoin estimation in management of childhood epilepsy. Arch Dis Child. 1971 Jun;46(247):386–388. doi: 10.1136/adc.46.247.386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Gerber N., Wagner J. G. Explanation of dose-dependent decline of diphenylhydantoin plasma levels by fitting to the integrated form of the Michaelis-Menten equation. Res Commun Chem Pathol Pharmacol. 1972 May;3(3):455–466. [PubMed] [Google Scholar]
  4. KUTT H., WINTERS W., KOKENGE R., MCDOWELL F. DIPHENYLHYDANTOIN METABOLISM, BLOOD LEVELS, AND TOXICITY. Arch Neurol. 1964 Dec;11:642–648. doi: 10.1001/archneur.1964.00460240074010. [DOI] [PubMed] [Google Scholar]
  5. Kaplan S. A., Jack M. L., Alexander K., Weinfeld R. E. Pharmacokinetic profile of diazepam in man following single intravenous and oral and chronic oral administrations. J Pharm Sci. 1973 Nov;62(11):1789–1796. doi: 10.1002/jps.2600621111. [DOI] [PubMed] [Google Scholar]
  6. Kariks J., Perry S. W., Wood D. Serum folic acid and phenytoin levels in permanently hospitalized epileptic patients receiving anticonvulsant drug therapy. Med J Aust. 1971 Aug 14;2(7):368–371. doi: 10.5694/j.1326-5377.1971.tb50600.x. [DOI] [PubMed] [Google Scholar]
  7. Kutt H., McDowell F. Management of epilepsy with diphenylhydantoin sodium. Dosage regulation for problem patients. JAMA. 1968 Mar 11;203(11):969–972. [PubMed] [Google Scholar]
  8. Kutt H., Verebely K. Metabolism of diphenylhydantoin by rat liver microsomes. I. characteristics of the reaction. Biochem Pharmacol. 1970 Mar;19(3):675–686. doi: 10.1016/0006-2952(70)90230-3. [DOI] [PubMed] [Google Scholar]
  9. Shuttleworth E., Wise G., Paulson G. Choreoathetosis and diphenylhydantoin intoxication. JAMA. 1974 Nov 25;230(8):1170–1171. [PubMed] [Google Scholar]
  10. Vajda F. J., Prineas R. J., Lovell R. R. Interaction between phenytoin and the benzodiazepines. Br Med J. 1971 Feb 6;1(5744):346–346. doi: 10.1136/bmj.1.5744.346-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. van der Klejin E., van Rossum J. M., Muskens E. T., Rijntjes N. V. Pharmacokinetics of diazepam in dogs, mice and humans. Acta Pharmacol Toxicol (Copenh) 1971;29 (Suppl 3):109–127. doi: 10.1111/j.1600-0773.1971.tb03291.x. [DOI] [PubMed] [Google Scholar]

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