title: Drug interaction between phenytoin and valproic acid in a child with refractory epilepsy: a case report.
abstract: BACKGROUND
  There are no published reports on pediatric phenytoin toxicity, resulting from the drug interaction between phenytoin and valproic acid.
  
  
  METHODS
  A 12-year-old patient with refractory epilepsy syndrome presented with phenytoin toxicity, following a concomitant treatment with phenytoin, valproic acid, and lamotrigine. The phenytoin concentration detected in the capsules used by the patient was in accordance with the prescribed dose and was appropriate for the age and weight of the patient. However, a supratherapeutic phenytoin serum concentration was observed (21.92 µg phenytoin/mL of blood). Consequently, the phenytoin dose was reduced, and the patient was monitored; 24 hours later the patient did not present with any signs/symptoms of toxicity.
  
  
  CONCLUSIONS
  Despite the appropriate phenytoin concentration in the capsules, the patient presented with phenytoin toxicity. This toxicity likely resulted from the drug interaction between phenytoin and valproic acid that leads to phenytoin displacement from plasmatic proteins and inhibits phenytoin metabolism, thereby increasing the concentration of free drug in the serum.
authors.affiliation: Department of Clinical Pathology, Faculty of Medical Sciences, University of Campinas, Campinas, Brazil.
authors.forename: Indira Valadê
authors.initials: IV
authors.lastname: Carvalho
authors.forename: Renata Cavalcanti
authors.initials: RC
authors.lastname: Carnevale
authors.forename: Marília Berlofa
authors.initials: MB
authors.lastname: Visacri
authors.forename: Priscila Gava
authors.initials: PG
authors.lastname: Mazzola
authors.forename: Rosiane
authors.initials: R
authors.lastname: de Fátima Lopes Ambrósio
authors.forename: Marcelo Conrado
authors.initials: MC
authors.lastname: dos Reis
authors.forename: Rachel Alvarenga
authors.initials: RA
authors.lastname: de Queiroz
authors.forename: Patricia
authors.initials: P
authors.lastname: Moriel
mesh_terms: D000927:Anticonvulsants / Q000097:blood* / Q000627:therapeutic use; D002648:Child; D004347:Drug Interactions / Q000502:physiology; D004827:Epilepsy / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D010672:Phenytoin / Q000097:blood* / Q000627:therapeutic use; D014635:Valproic Acid / Q000097:blood* / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid; D010672:Phenytoin
keywords: pediatrics; phenytoin; valproic acid