weight valproic

We prospectively examined the effect of antiepileptic (AED) cotherapy on steady state plasma concentrations of perampanel (PMP) in epileptic patients. We classified AEDs as strong enzyme inducers (carbamazepine, phenobarbital, phenytoin, oxcarbazepine), not strong enzyme inducers/not inhibitors (levetiracetam, lamotrigine, topiramate, rufinamide, lacosamide, zonisamide, clobazam), and enzyme inhibitors (valproic acid [VPA]). The main outcome was the comparison of PMP plasma concentration to weight-adjusted dose ratio (C/D; [μg/mL]/mg kg-1  d-1 ) among comedication subgroups...

Since the inception of clinical teratology, the vast majority of scientific work has focused on identification of drugs and environmental agents causing malformations in humans as a dichotomous variable (i.e. yes or no), as well as the relative and absolute risks of such occurrences. Generally, the dose dependency of such events has not been investigated. With the establishment of large pregnancy databases, dose-dependence relationships are being uncovered for increasing numbers of medications, including valproic acid, carbamazepine, phenobarbital, lamotrigine, topiramate, and lithium...

PURPOSE: Although some drugs used in the treatment of epilepsy are known to affect body weight, the hormonal factors responsible have not been sufficiently described. The purpose of this study was to compare insulin, leptin, neuropeptide Y and ghrelin levels in children with epilepsy receiving monotherapy with topiramate (TPM) and valproic acid (VPA), the drugs whose effects on body weight have been most discussed, with those of a control group. METHOD: 48 patients (25 VPA, 23 TPM) aged between 6 and 15...

OBJECTIVE: Intellectual disability (ID) is associated with weight gain caused by antiepileptic drugs such as valproic acid. The present study analyzed the relationship between ID and weight loss caused by topiramate (TPM). METHODS: Seventy-eight patients with epilepsy (35 women, aged 18 to 70years) were enrolled in this prospective study. Body weight was measured before and 1, 6, 12, and 18months after initiation of TPM treatment. Both patients and caregivers were provided information about TPM-related weight loss...

PURPOSE: The objective of this work was to develop a population pharmacokinetic model for a prolonged-release granule formulation of valproic acid (VPA) in children with epilepsy and to determine the doses providing a VPA trough concentration (Ctrough ) within the target range (50-100 mg/L). METHODS: Ninety-eight children (1-17.6 years, 325 plasma samples) were included in the study. The model was built with NONMEM 7.3. The probability to obtain Ctrough between 50 and 100 mg/L was determined by the Monte Carlo simulations for doses of 20, 30, 40, and 60 mg/kg/day and body weights between 10 and 70 kg...

AIM: To estimate pharmacokinetic variability of lamotrigine (LTG) and its clinical significance. MATERIAL AND METHODS: One hundred patients, including 74 women, aged from 18 to 77 years (38.23±14.37 years), with focal epilepsy were examined. Monotherapy with LTG was administered to 54 patients, duotherapy to 46 patients (LTG and valproic acid combination to 27 patients, LTG and liver enzymes inducers to 19 patients). Patients underwent procedures of therapeutic drug monitoring (TDM)...

PURPOSE: This study aims to describe the incidence of adverse drug reactions (ADRs) in children receiving antiepileptic drugs (AEDs) and compare ADRs to the individual drugs when given as monotherapy. METHOD: Paediatric patients (≤18 years old) were enrolled for this prospective observational study over a 6-month period, between September 2015 and March 2016. Adverse reactions to antiepileptic drugs (AEDs) were elicited at the time of enrolment and after 3 months using the Paediatric Epilepsy Side Effects Questionnaire...

The imidazole-based H3R antagonist 2-18 with high in vitro H3R antagonist affinity, excellent in vitro selectivity profile, and high in vivo H3R antagonist potency was tested for its anticonvulsant effect in maximal electroshock (MES)-induced convulsions in mice having valproic acid (VPA) as a reference antiepileptic drug (AED). Additionally, H3R antagonist 2-18 was evaluated for its reproductive toxicity in the same animal species. The results show that acute systemic administration (intraperitoneal; i.p.) of H3R antagonist 2-18 (7...

BACKGROUND AND AIMS: In this study, we evaluate the performance of allometric concepts to predict the implications of age and size on the pharmacokinetics of lamotrigine, and assess the dose rationale across different age groups from 0.2 to 91 years. METHODS: An allometrically scaled pharmacokinetic model was developed using adolescent and adult data, taking into account the effect of comedications. Model parameters were then used to extrapolate lamotrigine pharmacokinetics to older adults (> 65 years), children (4-12 years) and infants and toddlers (0...

INTRODUCTION: A common animal model of ASD is the one induced by valproic acid (VPA), inducing epigenetic changes and oxidative stress. We studied the possible preventive effect of the methyl donor for epigenetic enzymatic reactions, S-adenosine methionine (SAM), on ASD like behavioral changes and on redox potential in the brain and liver in this model. METHODS: ICR albino mice were injected on postnatal day 4 with one dose of 300 mg/kg of VPA, with normal saline (controls) or with VPA and SAM that was given orally for 3 days at the dose of 30 mg/kg body weight...

PURPOSE: The aims of this study were to develop a population pharmacokinetic (PPK) model of lamotrigine (LTG) in Chinese epileptic children by using nonlinear mixed effects modeling (NONMEM) and to investigate the effects of valproic acid (VPA) and genetic polymorphisms of the major metabolizing enzymes (UGT1A4, UGT2B7) on the pharmacokinetics of LTG. METHODS: A total of 182 epileptic children who were treated with LTG as monotherapy or as part of combination therapy were included in this study as the model group, and 61 patients were included as the validation group...

AIMS: Population pharmacokinetics is an essential tool that helps guide individualized dosing regimens. The aims of this systematic review are to provide knowledge concerning population pharmacokinetics of valproic acid (VPA) and to identify factors influencing VPA pharmacokinetic variability. METHODS: PubMed and Embase databases were systematically searched from inception to June, 2017. Relevant articles from reference lists were also included. All population pharmacokinetic studies of VPA conducted in humans and that employed a nonlinear mixed effect modelling approach were included in this review...

Valproic acid (VPA) is a well-established therapeutic used in treatment of seizure and mood disorders as well as migraines and a known hepatotoxicant. About 50% of VPA users experience metabolic disruptions, including weight gain, hyperlipidemia, and hyperinsulinemia, among others. Several of these metabolic abnormalities are similar to the effects of circadian rhythm disruption. In the current study, we examine the effect of VPA exposure on the expression of core circadian transcription factors that drive the circadian clock via a transcription-translation feedback loop...

Growing evidence that cell-based therapies can improve recovery outcome in spinal cord injury (SCI) models substantiates their application for treatment of human with SCI. To address the effectiveness of these stem cells, potential candidates should be evaluated in proper SCI platform that allows direct real-time monitoring. In this study, the role of epidermal neural crest stem cells (EPI-NCSCs) was elucidated in an ex vivo model of SCI, and valproic acid (VPA) was administered to ameliorate the inhospitable context of injury for grafted EPI-NCSCs...

In cancer, epilepsy can be the manifestation of a primary brain tumour, metastatic disease, vascular or surgical complications, opportunistic infection or secondary to anti-tumour therapy. Seizures are frequently the first symptom of a brain tumour. The epilepsy is related to elevated extracellular glutamate stimulating NMDAand AMPA-receptors and to the formation of D-2HG which resembles glutamate in IDH1 mutated gliomas. Epilepsy as presenting sign is associated with a longer survival in low- and high- grade gliomas, particularly with the IDH1 mutation...

BACKGROUND: Valproic acid (VPA), one of the most important antiepileptic drugs (AEDs), is proved to be inevitable for epileptic pregnant women to limit the hazards of convulsions on the fetuses and mothers. Periconceptional folic acid supplementation was investigated to protect against several birth defects. However, its role against VPA cerebellar toxicity was not properly investigated. AIM: The present study was conducted to evaluate the protective effect of folic acid against VPA cerebellar neurotoxicity...

BACKGROUND: Increasing number of scientific reports have highlighted the role of histone acetylation/deacetylation in neurodegenerative conditions, including chemotherapy-induced cognitive dysfunction (also known as chemobrain). Multiple sources state that increased activity of histone deacetylases (HDACs) play a detrimental role in chemobrain. In the present study, sodium valproate, a well-known HDAC inhibitor, was explored for its neuroprotective potential against chemobrain development...

The design, synthesis, characterization and biological properties of a Pt(iv) complex containing the very active inhibitor of histone deacetylase (2-propynyl)octanoic acid, POA, as an axial ligand are reported here. The title complex, namely (OC-6-44)-acetatodiamminedichlorido(2-(2-propynyl)octanoato)platinum(iv), 1, containing POA in racemic or in enantiomeric forms, was one/two orders of magnitude more active than cisplatin, depending on the chemo-sensitivity of the cancer cell lines. Moreover, 1 exhibited similar or even better antiproliferative activity than (OC-6-33)-diamminedichloridobis(2-propylpentanoato)platinum(iv), 2, containing two molecules of the well-known histone deacetylase inhibitor 2-propylpentanoic (valproic) acid...

BACKGROUND: Weight gain is a common adverse effect of sodium valproic acid (VPA) in children with epilepsy. Several mechanisms of VPA-induced obesity have been suggested such as increased appetite, facultative thermogenesis, and elevated insulin and leptin levels. In this study, we aimed to investigate the role of Insulin and Leptin in the pathogenesis of weight gain caused by VPA. MATERIALS AND METHODS: Body mass index (BMI) was calculated, and serum insulin and leptin levels were measured in 45 consecutive patients and 45 controls...

PURPOSE: The aim of the study is to evaluate the association between genetic polymorphisms and valproic acid (VPA) concentration to dose ratio in children with epilepsy on VPA monotherapy. METHODS: A total of 137 children, aged 3.5-18 years, (89 males and 48 females) with epilepsy on sustained-release VPA monotherapy were enrolled. Trough plasma concentrations of VPA at steady-state were measured using an AXSYM automatic immunity analyzer. The values were divided by body weight and total daily dose to calculate concentration to dose ratio of VPA (CDRV)...