1043-3155 Pediatr Neurol Briefs pedneurbriefs Pediatr Neurol Briefs Pediatric Neurology Briefs Pediatr Neurol Briefs 2166-6482 1043-3155 2166-3155 Pediatric Neurology Briefs Publishers Chicago, IL, USA PNB-6-53-a 10.15844/pedneurbriefs-6-7-7 Anticonvulsant Drugs Neurology Pediatrics Nervous System Diseases Child Development Brain Diseases Neurosurgery Child Infant Valproate Metabolites and Hyperammonemia http://orcid.org/0000-0002-0173-7931 Millichap J. Gordon MD 1 2 * Division of Neurology, Children's Memorial Hospital, Chicago, IL Departments of Pediatrics and Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL Correspondence: Dr. J. Gordon Millichap, E-mail: jgmillichap@northwestern.edu 07 1992 01 07 2016 6 7 53 53 Copyright: © 1992 The Author(s) 1992 This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Is 2-propyl-4-pentonoic acid (4-en), a hepatotoxic metabolite of valproate, responsible for valproateinduced hyperammonemia?

The association between valproate metabolism (VPA) and VPA induced hyperammonemia was studied at Hirosaki University Hospital, Japan.

 Valproate Metabolism Hyperammonemia Phenobarbital

The association between valproate metabolism (VPA) and VPA induced hyperammonemia was studied at Hirosaki University Hospital, Japan. In 53 monopharmacy patients, plasma NH3 levels did not depend on age, VPA dosage or serum levels and showed a negative correlation with the 4-en metabolite of VPA. In polypharmacy patients, plasma NH3 levels were significantly higher, while 2-en VPA serum level and bilirubin were lower than in monopharmacy patients. [1]

COMMENT. This study indicates that young age and high VPA serum levels are not risk factors for hyperammonemia induced by VPA and 4-en metabolite is not causally related to this adverse effect. These authors had previously reported that young age, polypharmacy, and high VPA serum level enhance the susceptibility to VPA hepatotoxicity by altering the metabolism of VPA and by increasing the conversion of VPA to 4-en, the most toxic VPA metabolite (see Ped Neur Briefs March 1992, 6:21).

In 43 children with epilepsy who were treated with VPA monotherapy or polytherapy, serum levels of copper were significantly lower than in normal control patients, whereas serum zinc levels were not altered. [2]

Valproate and carbamazepine, and in a lesser frequency, phenytoin and phenobarbital, were the most common causes of red blood cell macrocytosis in children in a study from the Children’s Medical Center, Dallas, TX [3]. Macrocytosis and pancytopenia may be the first manifestation of bone marrow failure and aplastic anemia. An MCV of more than 90 fL in a patient taking antiepileptic medications deserves careful monitoring.

 Kondo T Ishida M Kaneko S Hirano T Otani K Fukushima Y Is 2-propyl-4-pentonoic acid (4-en), a hepatotoxic metabolite of valproate, responsible for valproateinduced hyperammonemia? Epilepsia 1992 May-Jun 33 3 550 554 10.1111/j.1528-1157.1992.tb01708.x 1350534 Kaji M Ito M Okuno T Momoi T Sasaki H Yamanaka C Serum copper and zinc levels in epileptic children with valproate treatment Epilepsia 1992 May-Jun 33 3 555 557 10.1111/j.1528-1157.1992.tb01709.x 1592036 Pappo AS Fields BW Buchanan GR Etiology of red blood cell macrocytosis during childhood: impact of new diseases and therapies Pediatrics 1992 Jun 89 6 Pt 1 1063 1067 1534402