Effect of sodium valproate monotherapy on serum uric acid concentrations in ambulatory epileptic children: A prospective long-term study

Attilakos, Achilleas; Voudris, Konstantinos; Garoufi, Anastasia; Mastroyianni, Sotiria; Dimou, Stamatia; Prassouli, Alexia; Katsarou, Eustathia

doi:10.1016/j.ejpn.2006.09.002

Cited by 13 publications

(7 citation statements)

References 14 publications

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“…Hyperuricemia may increase superoxide production, stimulate vascular smooth cell proliferation, and upregulate the expression of plateletderived growth factor or monocyte chemoattractant protein-1, leading to damages of endothelial cells that cause atherosclerosis (Rao et al, 1991;Bos et al, 2006). Although the effect of AEDs on serum uric acid concentrations is controversial (Ring et al, 1991;Attilakos et al, 2006b;Aycicek & Iscan, 2007), our results showed that uric acid level was significantly higher in patients with VPA monotherapy. On the other hand, PHT, CBZ, or LTG did not elicit significant effect on the metabolism of uric acid.…”

Section: Discussionmentioning

confidence: 63%

Effects of long‐term antiepileptic drug monotherapy on vascular risk factors and atherosclerosis

et al. 2011

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Summary Purpose: Long‐term therapy with antiepileptic drugs (AEDs) has been associated with metabolic consequences that lead to an increase in risk of atherosclerosis in patients with epilepsy. We compared the long‐term effects of monotherapy using different categories of AEDs on markers of vascular risk and the atherosclerotic process. Methods: One hundred sixty adult patients who were receiving AED monotherapy, including two enzyme‐inducers (carbamazepine, CBZ; and phenytoin, PHT), an enzyme‐inhibitor (valproic acid, VPA), and a noninducer (lamotrigine, LTG) for more than 2 years, and 60 controls were enrolled in this study. All study participants received measurement of common carotid artery (CCA) intima media thickness (IMT) by B‐mode ultrasonography to assess the extent of atherosclerosis. Other measurements included body mass index, and serum lipid profile or levels of total homocysteine (tHcy), folate, uric acid, fasting blood sugar, high sensitivity C‐reactive protein (hs‐CRP), or thiobarbituric acid reactive substances (TBARS). Key Findings: Long‐term monotherapy with older‐generation AEDs, including CBZ, PHT, and VPA, caused significantly increased CCA IMT in patients with epilepsy. After adjustment for the confounding effects of age and gender, the CCA IMT was found to be positively correlated with the duration of AED therapy. Patients with epilepsy who were taking enzyme‐inducing AED monotherapy (CBZ, PHT) manifested disturbances of cholesterol, tHcy or folate metabolism, and elevation of the inflammation marker, hs‐CRP. On the other hand, patients on enzyme‐inhibiting AED monotherapy (VPA) exhibited an increase in the levels of uric acid and tHcy, and elevation of the oxidative marker, TBARS. However, no significant alterations in the markers of vascular risk or CCA IMT were observed in patients who received long‐term LTG monotherapy. Significance: Patients with epilepsy who were receiving long‐term monotherapy with CBZ, PHT, or VPA exhibited altered circulatory markers of vascular risk that may contribute to the acceleration of the atherosclerotic process, which is significantly associated the duration of AED monotherapy. This information offers a guide for the choice of drug in patients with epilepsy who require long‐term AED therapy, particularly in aged and high‐risk individuals.

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Section: Discussionmentioning

confidence: 63%

Effects of long‐term antiepileptic drug monotherapy on vascular risk factors and atherosclerosis

et al. 2011

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“…Thus, hypoglycemia in VPA exposed infants results from decreased gluconeogenesis and reduced liver glycogen and/or impaired glycogenolysis (4). Transient mild elevations of ALT, AST and LDH were found in children on VPA monotherapy (18, 19). Both VPA and PH may increase serum AST, ALT, and LDH levels (20).…”

Section: Discussionmentioning

confidence: 99%

Neonatal episodic hypoglycemia: A finding of valproic acid withdrawal

Çoban

Kurtoğlu²,

Akın³

et al. 2010

jcrpe

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The treatment of epilepsy during pregnancy is a worldwide problem. Drugs need to be used to control seizures in the mothers. In utero, exposure to valproic acid (VPA) and phenytoin (PH) may cause congenital malformations and also withdrawal symptoms such as irritability, jitteriness and symptoms of hypoglycemia. We present here a newborn with episodic hypoglycemia due to in utero exposure to VPA and PH. The mother was diagnosed as having complex partial epilepsy and was treated with PH (200 mg/day) and VPA (600 mg/day). The offspring developed jitteriness on the second day of life. The infant was hypoglycemic (32 mg/dl). These findings were accepted as withdrawal symptoms, since serum levels of VPA and PH were 37.8 μg/ml (50−100 μg/ml) and 6.37 μg/dl (10−20 μg/ml), respectively. Measurement of blood glucose is important and should be carefully monitored in infants exposed to antiepileptics in utero.Conflict of interest:None declared.

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“…It is an enzyme located on the outer surface of the cell membrane in many tissues, mainly in the liver, kidney, and pancreas, and is expressed in all cells except red blood cells [14]. Many studies have shown that long-term use of sodium valproate causes abnormal liver function [14][15][16][17]. For example, even when the drug concentration in blood can be maintained within the effective concentration range of 50-100 μg/mL, c-glutamyltransferase levels still increase [15].…”

Section: Discussionmentioning

confidence: 99%

“…Many studies have shown that long-term use of sodium valproate causes abnormal liver function [14][15][16][17]. For example, even when the drug concentration in blood can be maintained within the effective concentration range of 50-100 μg/mL, c-glutamyltransferase levels still increase [15]. Attilakos et al reported that the blood concentration of sodium valproate in patients taking the drug alone was maintained at 50-100 mg/ L during treatment, and the c-glutamyltransferase levels in children increased after 6, 12, and 24 months [15].…”

Section: Discussionmentioning

confidence: 99%

“…For example, even when the drug concentration in blood can be maintained within the effective concentration range of 50-100 μg/mL, c-glutamyltransferase levels still increase [15]. Attilakos et al reported that the blood concentration of sodium valproate in patients taking the drug alone was maintained at 50-100 mg/ L during treatment, and the c-glutamyltransferase levels in children increased after 6, 12, and 24 months [15]. Interestingly, the average level of c-glutamyltransferase in children with low concentrations of valproic acid was 14.4 (11.88, 18.72), which was signifcantly lower (p � 0.001) than that in children with normal concentrations of valproic acid 16 (12.9, 22).…”

Section: Discussionmentioning

confidence: 99%

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Development and Internal Validation of Machine Learning Algorithms for Determining Sodium Valproate Concentrations below the Standard Level Using a Risk Prediction Model of Children with Epilepsy

Yao,

Zhao,

Wang

et al. 2023

Journal of Clinical Pharmacy and Therapeutics

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Background. There is a narrow therapeutic window for sodium valproate, and the blood concentration is too low to control epilepsy, while it is easy to poison the body if the concentration is too high. It is therefore necessary to monitor drug concentration reasonably in order to control epilepsy. The purpose of this study was to establish a model for predicting concentrations of sodium valproate below 50 μg/mL in children with epilepsy. Methods. The clinical data and biochemical examination results of children with epilepsy treated in the pediatric outpatient department of our hospital from June 2019 to March 2022 were retrospectively collected and divided into a development group and a validation group according to a patient ratio of 8 to 2. Five machine learning algorithms were used to identify the key variable factors, and a risk prediction model for sodium valproate blood concentrations lower than the standard concentration was established. The area under the curve (AUC), calibration curve, GiViTi calibration band, and clinical influence curve were used to evaluate the diagnostic efficacy and clinical application value of the model. Results. A total of 525 children with epilepsy were enrolled. In the development group, the random forest algorithm performed best in predicting that the blood concentration of sodium valproate was lower than the standard concentration, showing the highest AUC (1.00). Six factors were determined as a nomogram to predict the incidence of low concentrations. In the validation group and the development group, the calibration curve, GiViTi calibration band, and clinical influence curve all performed well in the evaluation of the diagnostic efficacy and clinical application value of the model. Conclusions. This finding highlights the importance of examining biochemical indices in patients when data regarding the blood concentration of sodium valproate are lacking.

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Effect of sodium valproate monotherapy on serum uric acid concentrations in ambulatory epileptic children: A prospective long-term study

Cited by 13 publications

References 14 publications

Effects of long‐term antiepileptic drug monotherapy on vascular risk factors and atherosclerosis

Effects of long‐term antiepileptic drug monotherapy on vascular risk factors and atherosclerosis

Neonatal episodic hypoglycemia: A finding of valproic acid withdrawal

Development and Internal Validation of Machine Learning Algorithms for Determining Sodium Valproate Concentrations below the Standard Level Using a Risk Prediction Model of Children with Epilepsy

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