Pharmacokinetics and Clinical Utility of Valproic Acid Administered via Continuous Infusion

Cook, Aaron M.; Zafar, Muhammad; Mathias, Sally; Stewart, Alejandra M.; Albuja, Ana C.; Bensalem‐Owen, Meriem; Kapoor, Siddharth; Baumann, Robert J.

doi:10.1007/s40263-015-0304-5

Cited by 12 publications

(2 citation statements)

References 18 publications

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“…It seems that our research contained a larger sample size and much broader considerations of factors compared to other studies ( Chen et al, 2015 ; Zhu et al, 2018 ). Since TDM of the total serum concentrations of AEDs remains one of the primary methods for measuring drug efficacy indirectly ( Cook et al, 2016 ), it is not enough for researchers only focus on serum concentration. Jacob et al claim that standardized studies should be designed to assess concentration–efficacy–toxicity relationships when AEDs are urgently required ( Jacob and Nair, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Factors Impacting the Efficacy of Single or Combination Therapies of Valproic Acid, Carbamazepine, and Oxcarbazepine: A Longitudinal Observation Study

Peng

et al. 2021

Front. Pharmacol.

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Objective: This study aimed to determine the efficacy and clinical factors related to the pharmacodynamics of single or combination therapies of valproic acid (VPA), carbamazepine (CBZ), and oxcarbazepine (OXC), three commonly used anti-epileptic drugs (AEDs) in China.Methods: The study evaluated the records of 2027 outpatients in a Changsha hospital, located in China, from December 23, 2015 to October 28, 2019. The baseline seizure frequency was assessed during the first visit. AED efficacy was determined based on the reduction in seizures from baseline at the subsequent visits. Multivariable ordinal regression analysis was used to determine the association between the clinical factors (demographic characteristics, clinical features, and medication situation) and AED efficacy. For validation, the clinical efficacies of AEDs were compared as both single agents and in combinations. Differences in adverse effect (AEs) categories were analyzed by Chi-square between AED groups.Results: Records of patients receiving VPA, CBZ, and OXC were evaluated. Serum concentrations of VPA and CBZ is significantly correlated with efficacy (OR 1.030 [1.024–1.037], p < 0 0.0001; OR 1.250 [1.146–1.63], p < 0.0001, respectively) and OXC efficacy correlated to the serum concentration of the metabolite 10,11-dihydro-10-hydroxy-carbazepine (monohydroxy derivative, MHD) serum concentrations (OR 1.060 [1.031–1.089], p < 0.0001). Significant differences existed between females and males in VPA efficacy (OR 1.318 [1.033–1.682], p = 0.027). After validation, VPA, in combination with OXC (OR 1.93 [1.38–2.70], p<0.001), or with VGB (Vigabatrin) (OR 2.36 [1.38–2.70], p = 0.002), showed significantly better efficacy than as a single agent. OXC efficacy was also affected by the duration of epilepsy (OR 0.965 [0.946–0.984], p < 0.001). Additionally, the efficacies of OXC and VPA were also affected by the seizure type. Seizure reduction improved significantly with an increasing number of pharmacists’ educations in the first three visits period. There were no differences in AEs incidence among these 3 AEDs except for Psychiatric (0.02) and nervous system disorders (0.0001).Conclusion: Serum concentrations of VPA and CBZ may positively affect their efficacies, while OXC efficacies are correlated to MHD serum concentrations. The efficacy of VPA was higher in females compared to males. VPA-OXC and VPA-VGB combinations had higher efficacies compared to monotherapy. Besides, OXC efficacy is probably reducing by the duration of epilepsy. Additionally, VPA efficacy for focal or generalized seizures is superior to mixed-type seizures. OXC was more effective for focal seizures compared to mixed-type ones. Education provided by pharmacists improved the seizures to some extent, and there were no significant differences between most categories of adverse effects for the investigated AEDs.

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Section: Discussionmentioning

confidence: 99%

Evaluation of Factors Impacting the Efficacy of Single or Combination Therapies of Valproic Acid, Carbamazepine, and Oxcarbazepine: A Longitudinal Observation Study

Peng

et al. 2021

Front. Pharmacol.

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“…Patients with inadequate response, doubtful compliance, intercurrent illness, significant comorbidity, presence of interacting medications and so on can benefit from TDM ( Baumann et al, 2004 ; Patsalos et al, 2008 ). The recommended VPA therapeutic range for the epilepsy therapy is 50.0–100 μg/ml and the total concentration is usually measured clinically as a reference for treatment ( Gu et al, 2021 ) , ( Cook et al, 2016 ) .…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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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A population pharmacokinetic model taking into account protein binding for the sustained-release granule formulation of valproic acid in children with epilepsy

Rodrigues

Chhun

Chiron

et al. 2018

Eur J Clin Pharmacol

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Pharmacokinetics and Clinical Utility of Valproic Acid Administered via Continuous Infusion

Abstract: Continuous infusion valproic acid appears to be a safe, effective, and predictable manner by which to administer valproic acid to pediatric and adult patients admitted to the hospital.

Cited by 12 publications

References 18 publications

Evaluation of Factors Impacting the Efficacy of Single or Combination Therapies of Valproic Acid, Carbamazepine, and Oxcarbazepine: A Longitudinal Observation Study

Evaluation of Factors Impacting the Efficacy of Single or Combination Therapies of Valproic Acid, Carbamazepine, and Oxcarbazepine: A Longitudinal Observation Study

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

A population pharmacokinetic model taking into account protein binding for the sustained-release granule formulation of valproic acid in children with epilepsy

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