title: Antiepileptic drugs in patients with malignant brain tumor: beyond seizures and pharmacokinetics.
abstract: In neurological malignancies, antiepileptic drugs (AEDs) are frequently used to control the seizure activity that accompanies the disorder. There is a growing body of evidence on the importance of AED selection for reasons other than pharmacokinetics (PK) properties. Epigenetic modifications may occur in glioblastomas, such as changes in gene methylation and histone acetylation states. Secondary mechanisms of AED drug action which impact these epigenetic modifications could play a significant role in patient survival outcomes. Both valproic acid (VPA) and carbamazepine have histone deacetylase (HDAC) inhibitory activities, and levetiracetam and VPA reduce the activity of O6-methylguanine-DNA methyltransferase (MGMT), a DNA-repair molecule implicated in resistance to alkylating agents used for chemotherapy. The use of AEDs for purposes other than seizure prophylaxis and their selection based on non-PK properties present a potential paradigm shift in the field of neuro-oncology.
authors.affiliation: Pharmacy Practice Division, School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: H A
authors.initials: HA
authors.lastname: Gefroh-Grimes
authors.affiliation: School of Pharmacy & Department of Neurology, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: B E
authors.initials: BE
authors.lastname: Gidal
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D002220:Carbamazepine / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D000077287:Levetiracetam; D010889:Piracetam / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000627:therapeutic use; D012640:Seizures / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D014635:Valproic Acid / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D002220:Carbamazepine; D000077287:Levetiracetam; D014635:Valproic Acid; D010889:Piracetam
keywords: antiepileptic drugs; carbamazepine; epigenetics; glioblastoma; histone deacetylase; levetiracetam; valproic acid