Urinary excretion of valproate metabolites in children and adolescents.
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.
Reith
D M
DM
Royal Children's Hospital, Brisbane, Queensland 4029, Australia. D.Reith@medicine.uq.edu.au
Andrews
J
J
Parker-Scott
S
S
Eadie
M J
MJ
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*
D000927:Anticonvulsants; D004338:Drug Combinations; D014227:Triazines; D014635:Valproic Acid; D000077213:Lamotrigine