Association of CYP2C9, CYP2A6, ACSM2A, and CPT1A gene polymorphisms with adverse effects of valproic acid in Chinese patients with epilepsy

VPA is a branched short-chain fatty acid that is widely used as a first-line antiepileptic drug. Because of its narrow therapeutic concentration (50 –100μgmL−1), therapeutic drug monitoring is common. There are at least three routes of VPA metabolism in humans: β-oxidation in the mitochondria, cytochrome P450(CYP)-mediated oxidation of phase I and glucuronidation of phase II. Hepatotoxicity is the most serious adverse reaction to VPA. The current understanding of VPA hepatotoxicity involves VPA and its unsaturated metabolite 4-ene-VPA, which is activated by ligation to fatty acyl coenzyme A (CoA) via the medium chain acyl-coenzyme A synthetase (ACSM), and then transferred into the mitochondrial matrix with the help of carnitine palmi toyl transferase (CPT).
Source: Epilepsy Research - Category: Neurology Authors: Source Type: research