Urinary excretion of valproate metabolites in children and adolescents

The objective of this communication is to describe the changes in the metab olic profile of valproic acid (VPA) from early to late childhood and adoles cence. A cross-sectional study of 12 children and adolescents attending a n eurological outpatients department, who were medicated with VPA, was carrie d out. The proportions of daily dose excreted as VPA-glucuronide 3-oxo-VPA and 4-OH-VPA were calculated by relating 24-h recovery of these metabolites from urine to daily VPA dose. VPA, 3-oxo-VPA and 2-en-valproic acid (2-en- VPA) were measured in trough serum samples. VPA and its metabolites were me asured using a capillary gas chromatography method. The proportion of daily dose recovered as VPA-glucuronide in children 10 years and younger was sma ller than in older children (p < 0.05). There were no differences between a ge groups in the recovery of the other measured metabolites. Lamotrigine (L TG) comedication was also associated with a higher proportion of VPA dose r ecovered as glucuronide (p < 0.01). LTG comedication had a stronger associa tion with a higher proportion of dose being recovered as VPA-glucuronide on multivariate analysis than did the age group (p = 0.001 versus p < 0.05). In conclusion, older children and adolescents, when compared with younger c hildren, and those comedicated with LTG excrete a higher proportion of VPA dose as VPA-glucuronide. Copyright (C) 2000 John Wiley & Sons, Ltd.