title: Use of multi-dose activated charcoal in phenytoin toxicity secondary to genetic polymorphism.
abstract: BACKGROUND
  Phenytoin is metabolised in the liver by cytochrome (CYP)2C9 and 2C19 enzymes. Due to saturation of enzyme capacity, the elimination half-life is prolonged at supratherapeutic levels. Genetic polymorphisms of CYP2C9 and 2C19 are reasonably common and further prolong the elimination of phenytoin. There are conflicting reports regarding whether multiple-dose activated charcoal (MDAC) significantly increases the clearance of phenytoin in poisoning.
  
  
  METHODS
  We present 3 patients with phenytoin toxicity and very slow elimination secondary to reduced CYP enzyme function from genetic polymorphisms. MDAC was used in two patients and led to rapid and large reductions in the measured elimination half-lives. This is contrasted with very prolonged elimination in a third patient who did not receive MDAC.
  
  
  CONCLUSIONS
  MDAC may play a role in the management of chronic phenytoin toxicity, especially in those with very slow endogenous elimination secondary to genetic polymorphisms.
authors.affiliation: Prince of Wales Hospital, Clinical Toxicology & Emergency Medicine , Barker St, Randwick, Sydney , Australia.
authors.forename: Betty S H
authors.initials: BS
authors.lastname: Chan
authors.forename: Kate
authors.initials: K
authors.lastname: Sellors
authors.forename: Angela L
authors.initials: AL
authors.lastname: Chiew
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Buckley
mesh_terms: D000368:Aged; D000927:Anticonvulsants / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000931:Antidotes / Q000627:therapeutic use*; D002606:Charcoal / Q000627:therapeutic use*; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D009223:Myotonic Dystrophy / Q000150:complications / Q000188:drug therapy; D010672:Phenytoin / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011110:Polymorphism, Genetic / Q000235:genetics; D012640:Seizures / Q000150:complications / Q000188:drug therapy
chemical_list: D000927:Anticonvulsants; D000931:Antidotes; D002606:Charcoal; D010672:Phenytoin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19
keywords: Anticonvulsant; CNS; Complications of poisoning; Metabolic; Pharmaceuticals