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 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 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 Switching Between LC-ESI-MS/MS and EMIT Methods for Routine TDM of Valproic Acid in Pediatric Patients With Epilepsy: What Clinicians and Researchers Need to Know

2021 ◽  
Vol 12 ◽  
Author(s):  
Ying Xia ◽  
Jia-Yi Long ◽  
Meng-Yuan Shen ◽  
Na Dong ◽  
Hong-Li Guo ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Clinical Practice ◽  
Pediatric Patients ◽  
Therapeutic Drug ◽  
Close Attention ◽  
Altman Plot ◽  
Enzymatic Assays ◽  
Esi Ms ◽  
Immunoassay Technique ◽  
Patients With Epilepsy

Background: Valproic acid (VPA) is a widely used antiseizure medication and its dosing needs to be tailored individually through therapeutic drug monitoring (TDM) to avoid or prevent toxicity. Currently, immune-enzymatic assays such as Enzyme Multiplied Immunoassay Technique (EMIT), and Liquid Chromatography (LC)-based techniques, particularly coupled to Electrospray Ionization Tandem Mass Spectrometry (LC–ESI-MS/MS), resulting a potential lack of concordance between laboratories.Methods: In this study, plasma VPA concentrations were determined for 711 pediatric patients with epilepsy by a routine EMIT assay and by a validated in-house LC-ESI-MS/MS method on the same group of samples, aimed to address the aforementioned concern. Consistency between two assays was evaluated using linear regression and Bland-Altman analysis.Results: The calibration curve was linear in the range of 5.00–300 μg/ml for LC-ESI-MS/MS method and 1.00–150 μg/ml for EMIT assay, respectively. The two methods were proven to be accurate with quality control samples. As a result, a significant correlation between two methods was obtained with a regression equation described as [EMIT]=1.214×[LC−ESI−MS/MS]+3.054 (r2 = 0.9281). Bland-Altman plot showed a mean bias of 14.5 μg/ml (95% confidence interval (CI) (−0.2, 29.2) and a mean increase of 27.8% (95% CI (3.3, 52.4) measured by EMIT assay more than that measured by LC-ESI-MS/MS method.Conclusion: In conclusion, two methods were closely correlated, but EMIT assay overestimate VPA levels in human plasma compared with LC-ESI-MS/MS method. Due to the observed significant discordance between the tested methods, switching from immunoassays to LC-based techniques for TDM of VPA deserves close attention and therapeutic range of 35.0–75.0 μg/ml may be feasible. However, further studies are needed to evaluate the eligibility of this alternative range in the clinical practice. Clinicians should be informed when switching the VPA quantitation methods during the clinical practice.

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