Impairment of phenytoin parahydroxylation as a cause of severe intoxication. 1983

F A de Wolff, and P Vermeij, and M D Ferrari, and O J Buruma, and D D Breimer

A case history is presented of a patient who developed a severe phenytoin intoxication on a "therapeutic" dose of 300 mg/day. This phenomenon could be ascribed to a poor oxidative metabolizing capacity of this patient for phenytoin, as demonstrated by a low para-hydroxyphenyl-phenylhydantoin to phenytoin ratio in the urine. To characterize the specificity of this metabolic defect, debrisoquine and antipyrine oxidation were also studied. Contrary to expectations, this patient was shown to be an extensive debrisoquine metabolizer; the antipyrine clearance was even higher than normal. These findings suggest that phenytoin para-hydroxylation is regulated by an oxidative enzyme complex different from those which oxidize debrisoquine and antipyrine.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008297 Male Males
D010672 Phenytoin An anticonvulsant that is used to treat a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. Diphenylhydantoin,Fenitoin,Phenhydan,5,5-Diphenylhydantoin,5,5-diphenylimidazolidine-2,4-dione,Antisacer,Difenin,Dihydan,Dilantin,Epamin,Epanutin,Hydantol,Phenytoin Sodium,Sodium Diphenylhydantoinate,Diphenylhydantoinate, Sodium
D003647 Debrisoquin An adrenergic neuron-blocking drug similar in effects to GUANETHIDINE. It is also noteworthy in being a substrate for a polymorphic cytochrome P-450 enzyme. Persons with certain isoforms of this enzyme are unable to properly metabolize this and many other clinically important drugs. They are commonly referred to as having a debrisoquin 4-hydroxylase polymorphism. Debrisoquine,Tendor
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006900 Hydroxylation Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed) Hydroxylations
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D000983 Antipyrine An analgesic and antipyretic that has been given by mouth and as ear drops. Antipyrine is often used in testing the effects of other drugs or diseases on drug-metabolizing enzymes in the liver. (From Martindale, The Extra Pharmacopoeia, 30th ed, p29) Phenazone,Anodynin,Pyramidone

Related Publications

F A de Wolff, and P Vermeij, and M D Ferrari, and O J Buruma, and D D Breimer
January 2015, American journal of therapeutics,
F A de Wolff, and P Vermeij, and M D Ferrari, and O J Buruma, and D D Breimer
May 1990, Journal of the neurological sciences,
F A de Wolff, and P Vermeij, and M D Ferrari, and O J Buruma, and D D Breimer
January 1990, DICP : the annals of pharmacotherapy,
F A de Wolff, and P Vermeij, and M D Ferrari, and O J Buruma, and D D Breimer
April 2007, Nederlands tijdschrift voor geneeskunde,
F A de Wolff, and P Vermeij, and M D Ferrari, and O J Buruma, and D D Breimer
January 2007, Nederlands tijdschrift voor geneeskunde,
F A de Wolff, and P Vermeij, and M D Ferrari, and O J Buruma, and D D Breimer
July 1975, Clinical pharmacology and therapeutics,
F A de Wolff, and P Vermeij, and M D Ferrari, and O J Buruma, and D D Breimer
November 1981, The Western journal of medicine,
F A de Wolff, and P Vermeij, and M D Ferrari, and O J Buruma, and D D Breimer
October 1985, Harefuah,
F A de Wolff, and P Vermeij, and M D Ferrari, and O J Buruma, and D D Breimer
January 2004, Neurology,
F A de Wolff, and P Vermeij, and M D Ferrari, and O J Buruma, and D D Breimer
January 2004, Neurology,
Copied contents to your clipboard!