title: Urinary excretion of valproate metabolites in children and adolescents.
abstract: The objective of this communication is to describe the changes in the metabolic profile of valproic acid (VPA) from early to late childhood and adolescence. A cross-sectional study of 12 children and adolescents attending a neurological outpatients department, who were medicated with VPA, was carried 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 measured using a capillary gas chromatograpy method. The proportion of daily dose recovered as VPA-glucuronide in children 10 years and younger was smaller than in older children (p<0.05). There were no differences between age groups in the recovery of the other measured metabolites. Lamotrigine (LTG) comedication was also associated with a higher proportion of VPA dose recovered as glucuronide (p<0.01). LTG comedication had a stronger association 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 children, and those comedicated with LTG excrete a higher proportion of VPA dose as VPA-glucuronide.
authors.affiliation: Royal Children's Hospital, Brisbane, Queensland 4029, Australia. D.Reith@medicine.uq.edu.au
authors.forename: D M
authors.initials: DM
authors.lastname: Reith
authors.forename: J
authors.initials: J
authors.lastname: Andrews
authors.forename: S
authors.initials: S
authors.lastname: Parker-Scott
authors.forename: M J
authors.initials: MJ
authors.lastname: Eadie
mesh_terms: D000293:Adolescent; D000375:Aging / Q000378:metabolism; D000927:Anticonvulsants / Q000652:urine*; D001711:Biotransformation; D002648:Child; D002675:Child, Preschool; D002849:Chromatography, Gas; D003430:Cross-Sectional Studies; D004338:Drug Combinations; D004347:Drug Interactions; D005260:Female; D006801:Humans; D006868:Hydrolysis; D000077213:Lamotrigine; D008297:Male; D014227:Triazines / Q000493:pharmacokinetics; D014635:Valproic Acid / Q000652:urine*
chemical_list: D000927:Anticonvulsants; D004338:Drug Combinations; D014227:Triazines; D014635:Valproic Acid; D000077213:Lamotrigine