Effect of Drug Therapy on the Metabolism of Phenytoin
It is common clinical experience that phenytoin is an unpredictable drug to use in practice. Some patients can tolerate doses of 600 mg daily or more without showing signs of drug intoxication, while others become intoxicated with 200 mg or less. On occasion, a patient who has been stabilized for months or years on a constant dose of the drug suddenly develops nystagmus and ataxia. In some patients who are being started on phenytoin therapy, the serum concentration of the drug often remains low despite gradually increasing doses, until suddenly a point is reached when it rises dangerously close to the toxic range with a further increment.
KeywordsNicotine Neurol Diazepam Chlordiazepoxide Phenobarbital
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- Gerber, N., Wagner, J. F.: Explanation of dose-dependent decline of diphenylhydantoin plasma levels by fitting to the integrated form of the Midiaelis-Menten equation. Res. Comm. Chem. Path. Pharmac. 3, 455 (1972).Google Scholar
- Houghton, G. W., Richens, A.: Rate of elimination of tracer doses of phenytoin at different steady-state serum concentrations in epileptic patients. Brit. J. clin. Pharmac. 1, 155 (1974 a).Google Scholar
- Houghton, G. W., Richens, A.: Inhibition of phenytoin metabolism by sulthiame in epileptic patients. Brit. J. clin. Pharmac. 1, 59 (1974 b).Google Scholar
- Houghton, G. W., Richens, A.: Phenytoin intoxication induced by sulthiame — a common clinical problem. In: Epilepsy Proceedings of Hans Berger Centenary Symposium, Edinburgh. Churchill Livingstone (1974 d).Google Scholar
- Kutt, H.: Diphenylhydantoin. Interactions with other drugs in man. In: Antiepileptic Drugs (Eds. D. M. Woodbury, J. K. Penry, R. P. Schmidt), p. 169. New York: Raven Press 1972.Google Scholar
- Mawer, G. E., Mullen, P. W., Rodgers, M., Robins, A. J., Lucas, S. B.: Phenytoin dose adjustment in epileptic patients. Brit. J. clin. Pharmac. 1, 163 (1974).Google Scholar
- Richens, A.: Drug estimation in the treatment of epilepsy. Proc. roy. Soc. Med. 67, 1227 (1974).Google Scholar
- Richens, A.: Results of a phenytoin quality control scheme. In: Clinical Pharmacology of Anti-Epileptic Drugs (Eds. H. Schneider, D. Janz, C. Gardner-Thorpe, H. Meinardi, A. L. Sherwin), p. 293. Berlin-Heidelberg-New York: Springer 1975.Google Scholar
- Vessell, E. S., Passananti, G. T., Greene, F. E.: Impairment of drug metabolism in man by allopurinol and nortriptyline. New Engl. J. Med. 283, 1484 (1970).Google Scholar