Abstracts

Animal studies have demonstrated that valproic acid (VPA) increases the hepatic and plasma levels of 15-F[sub]2t[/sub]-isoprostane (15-F[sub]2t[/sub]-IsoP), which is used as an in vivo marker of oxidative stress. It has been postulated that increased levels of reactive oxygen species may play a role in the pathogenesis of idiosyncratic VPA hepatotoxicity.
The objective of the study was to compare urinary 15-F[sub]2t[/sub]-IsoP levels in children receiving VPA with those in children receiving carbamazepine (CBZ) or clobazam. A morning urine sample was collected from patients younger than 16 years of age, receiving monotherapy with VPA (n=15), carbamazepine (CBZ) (n=13) or clobazam (n=6) for [ge] 4 weeks and from age-matched controls not receiving medications (n=31). Urine 15-F[sub]2t[/sub]-IsoP levels were determined by ELISA. The mean ([plusmn] SD) urine 15-F[sub]2t[/sub]-IsoP levels (nmol/mmol Cr) were: VPA (0.36 [plusmn] 0.17); CBZ (0.24 [plusmn] 0.10); clobazam (0.18 [plusmn] 0.01); control group (0.19 [plusmn] 0.09). Using one-way ANOVA with a Bonferonni[rsquo]s pairwise multiple comparison test, patients treated with VPA had significantly elevated 15-F[sub]2t[/sub]-IsoP levels when compared to the control, CBZ and clobazam groups (p[lt]0.05). There was no difference in 15-F[sub]2t[/sub]-IsoP levels between CBZ, clobazam and control groups. These data demonstrate that treatment of children with VPA is associated with increased urinary 15-F[sub]2t[/sub]-IsoP levels. The role of reactive oxygen species in the pathogenesis of VPA hepatotoxicity should be explored further. (Supported by Canadian Institutes of Health Research.)