Effects of valproate on acylcarnitines in children with epilepsy using ESI-MS/MS.
OBJECTIVE
To determine the influence of valproate (VPA) treatment on acylcarnitines in children with epilepsy.


METHODS
Determination of acylcarnitines (including free carnitine and acylcarnitines from C2 to C18) in dried blood spot specimens using tandem-mass spectrometry. Longitudinal study of changes in acylcarnitines in children under VPA treatment without pretreatment (group 1) or with pretreatment with other antiepileptic drugs (group 2) before the start of VPA treatment at an early and a late treatment interval (12-66, 90-260 days after the beginning of treatment, respectively). Cross-sectional comparison of these two VPA groups and of a group receiving carbamazepine monotherapy (group 3) with controls.


RESULTS
Acylcarnitines in epileptic patients before VPA therapy did not differ from control values. In group 1, decreases of C0 (-26%), C2 (-12%), C16 (-31%), C18 (-41%), C(total) (-10%), increases of C5OH (+31%), C8 (+33%) in the early treatment interval, and decreases of C16 (-21%), C18 (-42%), and increases of C2 (+26%), C5OH (+44%) in the late treatment interval were significant. In group 2, both in the longitudinal and the cross-sectional study, only a decrease of C18 (-41%, -43%, respectively) in the late treatment interval was found. In group 3, no significant changes have been observed.


CONCLUSIONS
We could prove changes in acylcarnitine subspecies, which were associated with VPA treatment in children with epilepsy. The treatment interval with the most marked changes coincides with the interval of highest risk for VPA-induced hepatotoxicity. The observed specific acylcarnitine pattern might point to the impaired intermediary metabolism that is responsible for VPA-induced hepatotoxicity.
Werner
Tamara
T
Department of Pediatrics, University Children's Hospital, Mannheim, Germany.
Treiss
Irmgard
I
Kohlmueller
Dirk
D
Mehlem
Peter
P
Teich
Martin
M
Longin
Elke
E
Gerstner
Thorsten
T
Koenig
Stephan A
SA
Schulze
Andreas
A
D000293:Adolescent; D000927:Anticonvulsants / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002220:Carbamazepine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004827:Epilepsy / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D014635:Valproic Acid / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000927:Anticonvulsants; C116917:acylcarnitine; D002220:Carbamazepine; D014635:Valproic Acid; D002331:Carnitine