Simultaneous determination of valproic acid and 2-propyl-4-pentenoic acid for the prediction of clinical adverse effects in Chinese patients with epilepsy

Introduction: Valproic acid (VPA) is an antiepileptic drug used to treat epilepsy and bipolar disorder. Adverse effects of VPA were studied in many reports, however, a dose-response relationship between VPA and its metabolites in epilepsy patients are extremely limited. In this paper, a high efficient method was developed for the preconcentration and determination of VPA and its main metabolite in plasma. Methods: For the extraction and preconcentration of the selected analytes, a volume of an extractant was placed at the bottom of the microtube containing pretreated plasma. The mixture was repeatedly withdrawn from the microtube and pushed-out into it using a 1.0-mL glass syringe and resulted in a cloudy mixture. For further turbidity, the mixture was shaken on a vortex agitator. This procedure was used to analyze the plasma samples of patients with epilepsy (n = 70). Results: The results revealed that in most patients with a low level of VPA relative to its expected level, 3-heptanone concentrations were high. The limits of quantification of 3-heptanone and VPA were 0.04 mg L–1 and 0.2 mg L–1, respectively. A suitable precision at a concentration of 2 mg L-1 for each analyte was obtained (relative standard deviation ≤ 9%). Conclusion: The obtained results indicated that this procedure is easy, sensitive, and reliable, and can be used for the analysis of the selected analytes in the plasma samples of patients with epilepsy.

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NCOG-45. FIRST-LINE ANTIEPILEPTIC DRUG TREATMENT IN GLIOMA PATIENTS WITH EPILEPSY: LEVETIRACETAM VERSUS VALPROIC ACID

Neuro-Oncology ◽

10.1093/neuonc/noaa215.583 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii139-ii139

Author(s):

Pim van der Meer ◽

Linda Dirven ◽

Marta Fiocco ◽

Maaike Vos ◽

Mathilde Kouwenhoven ◽

...

Keyword(s):

Valproic Acid ◽

Adverse Effects ◽

Treatment Failure ◽

Cumulative Incidence ◽

Treatment Initiation ◽

Risk Model ◽

First Line ◽

Recurrent Seizure ◽

Competing Risk Model ◽

Patients With Epilepsy

Abstract BACKGROUND Levetiracetam and valproic acid are two of the most commonly prescribed antiepileptic drugs (AEDs) in patients with a glioma and epilepsy. This study aimed at estimating the cumulative incidence of treatment failure of first-line monotherapy levetiracetam versus valproic acid in glioma patients with epilepsy. METHODS In this retrospective observational study, a competing risk model was used to estimate the cumulative incidence of treatment failure, from AED treatment initiation, for the two AEDs with death as competing event. Patients were matched on baseline covariates potentially related to treatment assignment and/or outcomes of interest according to the nearest neighbour propensity score matching technique. Secondary outcomes were the cumulative incidence of recurrent seizure, from AED treatment initiation (estimated with a competing risk model), and severity of adverse effects. Maximum duration of follow-up was 36 months. RESULTS In total, 776 patients using levetiracetam and 659 using valproic were identified. Matching resulted in two equal groups of 429 patients, with similar covariate distribution. The cumulative incidence of treatment failure (any reason) at 12 months for levetiracetam and valproic acid was equal to 33% (95%CI=29-38%) versus 50% (95%CI=45-55%), respectively (p< 0.001). The cumulative incidence of treatment failure due to uncontrolled seizures was significantly lower for levetiracetam compared to valproic acid (12 months: 16% [95%CI=12-19%] versus 28% [95%CI=23-32%]; p< 0.001), but no differences were found for treatment failure due to adverse effects (12 months: 14% [95%CI=11-18%] versus 15% [95%CI=11-18%]; p=0.636). The cumulative incidence of recurrent seizure of levetiracetam was significantly lower compared to valproic acid (12 months: 54% [95%CI=49-59%] versus 67% [95%CI=62-71%]; p< 0.001). No significant differences were found for level of toxicity. CONCLUSION Our results suggest that levetiracetam has superior efficacy compared to valproic acid, while showing a similar level of toxicity. Therefore, levetiracetam seems the preferred choice for first-line AED treatment in glioma patients.

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