scholarly journals Genetic and Non-genetic Factors Contributing to the Significant Variation in the Plasma Trough Concentration-to-Dose Ratio of Valproic Acid in Children With Epilepsy

2021 ◽  
Vol 8 ◽  
Author(s):  
Ze-Yue Xu ◽  
Hong-Li Guo ◽  
Ling Li ◽  
Min Zhang ◽  
Xia Jing ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Trough Concentration ◽  
Genetic Factors ◽  
Pediatric Patients ◽  
Oral Solution ◽  
Total Daily Dose ◽  
Nucleotide Polymorphisms ◽  
Dose Ratio ◽  
Control Effect ◽  
Patients With Epilepsy

Objective: This study was conducted to evaluate the potential genetic and non-genetic factors contributing to plasma trough concentration-to-dose (C0/D) ratio of valproic acid (VPA) in pediatric patients with epilepsy.Study Design: A single-center, retrospective cohort study was performed by collecting data from 194 children aged 1–14 years between May 2018 and November 2018. The oral solution (n = 135) group and the sustained-release (SR) tablet group (n = 59) were defined, and the plasma VPA C0 was measured. Twenty-six single-nucleotide polymorphisms (SNPs) were chosen for genotyping with the MassARRAY system. A multiple logistic regression model was used for data analysis.Results: Body weight (BW) and age were positively correlated with the C0/D ratio in 194 patients, but the positive correlation disappeared after the patients were divided into oral solution and SR tablet subgroups. The average C0/D ratio was significantly increased by 2.11-fold (P = 0.000) in children who took VPA SR tablets compared with children who were administered VPA oral solutions. No significant association between genetic variants and the C0/D ratio was found, even for the five well-studied SNPs, namely UGT2B7 G211T, C802T, C161T, T125C, and CYP2C9*3 A1075C. However, a significant association between the C0/D ratio and UGT1A6/9 Del>A (rs144486213) was observed in the VPA oral solution group, but not in the VPA SR tablet group.Conclusions: The dosage forms of sodium valproate, rather than BW, age, or genetic polymorphisms, significantly affected the VPA C0/D ratios in pediatric patients with epilepsy. Based on our findings, switching the dosage form between solution and SR tablet should be performed cautiously. Total daily dose adjustment should be considered, and the plasma concentration, seizure-control effect, and adverse drug reaction should also be monitored very closely.

scholarly journals CYP2C9*3/*3 Gene Expression Affects the Total and Free Concentrations of Valproic Acid in Pediatric Patients with Epilepsy

2021 ◽  
Vol Volume 14 ◽  
pp. 417-430
Author(s):  
Xikun Wu ◽  
Weichong Dong ◽  
Haoran Li ◽  
Xiuling Yang ◽  
Yiran Jin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Valproic Acid ◽  
Pediatric Patients ◽  
Patients With Epilepsy

No Effect of Gender or Age on Binding Characteristics of Valproic Acid to Serum Proteins in Pediatric Patients with Epilepsy

1999 ◽  
Vol 39 (10) ◽  
pp. 1070-1076 ◽  
Author(s):  
Yasuo Kodama ◽  
Hirofumi Kodama ◽  
Masae Kuranari ◽  
Kimiko Tsutsumi ◽  
Shunsuke Ono ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Pediatric Patients ◽  
Serum Proteins ◽  
Binding Characteristics ◽  
Patients With Epilepsy

scholarly journals Efficacy of levetiracetam monotherapy in epilepsy associated with benign epileptiform discharges of childhood

2019 ◽  
Vol 11 (1) ◽  
pp. 63-68 ◽  
Author(s):  
N. A. Borovkova ◽  
A. G. Malov
Keyword(s):  
Valproic Acid ◽  
Pediatric Patients ◽  
Slow Wave Sleep ◽  
Epileptiform Activity ◽  
Functional Tests ◽  
Antiepileptic Treatment ◽  
Epileptiform Discharges ◽  
First Choice ◽  
Eeg Recordings ◽  
Patients With Epilepsy

Aim. To analyze efficacy of levetiracetam monotherapy in patients with epilepsy associated with benign epileptiform discharges of childhood (BEDC). Materials and methods. We examined 29 pediatric patients with idiopathic and symptomatic BEDC-associated epilepsy, including continuous spike-and-wave epileptiform activity during slow-wave sleep (CSWS) in the stage of clinical remission. Of those, 12 children received antiepileptic treatment with valproic acid, and 17 children received levetiracetam. The examination included passive awake EEG recordings (with functional tests) as well as daytime sleep EEG recordings (within 60 minutes). Results. Levetiracetam was no less efficient in monotherapy of BEDC-associated epilepsy (including the CSWS patterns) than the traditionally used valproic acid, especially in idiopathic forms of epilepsy. Conclusion. Levetiracetam can be recommended for the first-choice basic anti-epileptic monotherapy treatment.

scholarly journals Association of SCN1A, SCN2A, and UGT2B7 Polymorphisms with Responsiveness to Valproic Acid in the Treatment of Epilepsy

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yuan Lu ◽  
Quanping Su ◽  
Ming Li ◽  
Alimu Dayimu ◽  
Xiaoyu Dai ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Genetic Factors ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
Metabolizing Enzymes ◽  
Single Nucleotide ◽  
Potential Association ◽  
Epileptic Patients ◽  
Snp Interaction

Purpose. The efficacy of valproic acid (VPA) varies widely in clinical treatment of epileptic patients. Our study is aimed at exploring a potential association between polymorphisms of SCN1A, SCN2A, and UGT2B7 genetic factors and VPA responses. Methods. In this observational study, a total of 114 epileptic patients only treated with VPA for at least 1 year were included to explore the genetic polymorphisms of drug responses (mean follow-up time: 3.68±1.78 years). Thirty-one single-nucleotide polymorphisms (SNPs) in three candidate genes that related with drug-metabolizing enzymes and receptors were genotyped. Results. Of the 31 SNPs, eight were significantly associated with VPA responses, including rs1381105, rs2162600, rs10197716, rs2119068, rs2119067, rs353116, rs353112 and rs6740895. The interaction between rs10197716 and rs2119068 was the most significantly correlated with VPA responses compared with other combinations (the highest VPA-responsive rate 0.92 versus the lowest VPA-responsive rate 0.33, p=0.007). Conclusion. The study indicated that eight SNPs and SNP-SNP interaction may be associated with VPA responses in Chinese Han epileptic patients. The SNPs were rs1381105 (SCN1A), rs2162600 (SCN1A), rs10197716 (SCN2A), rs2119068 (SCN2A), rs2119067 (SCN2A), rs353116 (SCN2A), rs353112 (SCN2A) and rs6740895 (SCN2A), respectively. The interaction between the three pairs of rs10197716-rs2119068, rs10197716-rs11889342 and rs7598931-rs12233719 was the most significant for VPA. This implied that these SNPs may play an important role in the pharmacogenomics mechanism of valproic acid.

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