ArticleBMC neurology2025
Valproic acid levels in neurodevelopmental disorders: correlation with CYP and SULT genes using LC-MS/MS.
Article in BMC neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundValproic acid (VPA) is one of the most widely prescribed antiepileptic drugs worldwide, which is used to treat migraines, bipolar disorder, and anxiety. However, VPA is associated with a wide range of side effects. This study evaluates therapeutic drug monitoring (TDM) in individuals with neurodevelopmental disorders. It explores the correlation between valproic acid (VPA) plasma levels and genetic polymorphisms in cytochrome P450 (CYP) enzymes and cytosolic sulfotransferase (SULT) genes.
methodsA simple and accurate LC-MS/MS method was developed, validated, and applied in the TDM of 14 individuals on VPA therapy. Plasma VPA levels were measured, and genotyped genes SULT1A1, CYP2D64, CYP2D610, CYP3A5, and CYP2C19*2. Statistical analyses were conducted using SPSS.
resultsOf the fourteen participants, two had toxic plasma VPA levels (≥ 100 µg/mL), one had a sub-therapeutic level (< 50 µg/mL), and eleven were within or slightly above the therapeutic range (50-100 µg/mL). No significant correlation was observed between VPA plasma concentrations and genotypes of SULT1A1 (p = 0.522), CYP2C192 (p = 0.288), CYP2D64 (p = 0.895), or CYP2D6*10 (p = 0.067). While no direct associations were found, genotype-guided drug therapy remains a promising strategy for optimizing drug efficacy and minimizing toxicity.
conclusionsThis study highlights the complexity of valproic acid (VPA) therapy in individuals with neurodevelopmental disorders and the limited influence of common genetic polymorphisms in CYP and SULT genes on VPA plasma levels. While therapeutic drug monitoring (TDM) remains an invaluable tool for optimizing VPA therapy, the lack of significant correlations between genetic variants and VPA concentrations suggests that routine pharmacogenetic testing for these specific variants may not be warranted in clinical practice. However, the observed toxic and sub-therapeutic VPA levels emphasize the importance of regular TDM to mitigate risks associated with overdose or insufficient dosing.
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