title: [Relationship between plasma concentrations of valproic acid and hepatotoxicity in patients receiving high doses].
abstract: BACKGROUND
  Valproic acid (VPA) is an anticonvulsivant drug widely prescribed in the treatment of many forms of generalized epilepsy. In literature, the incidence of liver damage induced by AVP is 0.01%. It is potentialized by the combination therapy (phenobarbital, carbamazepine). Severe hepatotoxicity is rare and appears to be independent of dose and to cause a high mortality.
  
  
  METHODS
  The aim of our study was to evaluate the relationship between plasma concentrations of AVP and the occurrence of side effects especially hepatotoxicity in patients receiving high doses of AVP.
  
  
  RESULTS
  In this period, 425 plasmatic AVP monitoring were carried out in our laboratory. From 128 patients treated by high doses of AVP, only 73 were included in this study. Our work showed that adverse effects in epileptics under high doses of AVP was related to the association of the AVP with other antiepileptic in particular carbamazépine, phenobarbital and benzodiazepines rather than supra-therapeutic plasmatic concentrations of AVP. The association of AVP to major antiepileptics (carbamazépine and or phenobarbital) does not seem to generate an increase in the plasmatic concentration of AVP, which was not associated with a greater risque of adverse effects.
  
  
  CONCLUSIONS
  Consequently, clinical signs of liver toxicity may be present in AVP concentrations generally considered in the therapeutic range especially when used in high doses and or combined with antiepileptic drugs like phenobarbital or carbamazepine.
authors.affiliation: Laboratoire de pharmacologie, faculté de médecine de Sfax, avenue Majida-Boulila, 3029 Sfax, Tunisie.
authors.forename: H
authors.initials: H
authors.lastname: Ghozzi
authors.forename: A
authors.initials: A
authors.lastname: Hakim
authors.forename: Z
authors.initials: Z
authors.lastname: Sahnoun
authors.forename: L
authors.initials: L
authors.lastname: Ben Mahmoud
authors.forename: R
authors.initials: R
authors.lastname: Atheymen
authors.forename: S
authors.initials: S
authors.lastname: Hammami
authors.forename: K
authors.initials: K
authors.lastname: Zeghal
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D001663:Bilirubin / Q000097:blood; D002220:Carbamazepine / Q000009:adverse effects; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016903:Drug Monitoring; D004827:Epilepsy / Q000150:complications / Q000188:drug therapy; D005260:Female; D006801:Humans; D007223:Infant; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D010634:Phenobarbital / Q000009:adverse effects; D018570:Risk Assessment; D014635:Valproic Acid / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D002220:Carbamazepine; D014635:Valproic Acid; D001663:Bilirubin; D010634:Phenobarbital