Effects of food on valproic acid absorption

Hamilton, Robert A.; Garnett, William R.; Kline, Berry J.; Pellock, John M.

doi:10.1093/ajhp/38.10.1490

Cited by 7 publications

(7 citation statements)

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“…This is consistent with the observation that VPA promotes DAT expression since increased DAT expression will lead to increased DA reuptake which in turn results in decreased DA release into the media. Serum VPA concentration has been studied previously; on average, a dose of 250 mg VPA induces a serum concentration of 54.6 lg/mL (0.34 mM) (Hamilton et al 1981), which is comparable to our tested concentration (0.6 mM) and this and higher doses are well tolerated (Atmaca et al 2007). In summary, taken together, the data support the feasibility of testing VPA for future drug addiction treatment.…”

Section: Discussionsupporting

confidence: 81%

Using iPSC‐derived human DA neurons from opioid‐dependent subjects to study dopamine dynamics

et al. 2016

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IntroductionThe dopaminergic (DA) system plays important roles in addiction. However, human DA neurons from drug‐dependent subjects were not available for study until recent development in inducible pluripotent stem cells (iPSCs) technology.MethodsIn this study, we produced DA neurons differentiated using iPSCs derived from opioid‐dependent and control subjects carrying different 3′ VNTR (variable number tandem repeat) polymorphism in the human dopamine transporter (DAT or SLC6A3). In addition, the effects of valproic acid (VPA) exposures on iPSC‐derived human DA neurons are also examined.ResultsWe present the first evidence suggesting that the 3′ VNTR polymorphism in the hDAT gene affects DAT expression level in iPSC‐derived human DA neurons. In human DA neurons, which provide an appropriate cellular milieu, VPA treatment alters the expression of several genes important for dopaminergic neuron function including DAT, Nurr1, and TH; this might partly explain its action in regulating addictive behaviors. VPA treatment also significantly increased DA D2 receptor (Drd2) expression, especially in the opioid‐dependent iPSC cell lines.ConclusionsOur data suggest that human iPSC‐derived DA neurons may be useful in in vitro experimental model to examine the effects of genetic variation in gene regulation, to examine the underlying mechanisms in neurological disorders including drug addiction, and to serve as a platform for therapeutic development.

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Section: Discussionsupporting

confidence: 81%

Using iPSC‐derived human DA neurons from opioid‐dependent subjects to study dopamine dynamics

et al. 2016

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“…An intravenous formulation is also available. Food coingestion can delay absorption but not the extent of absorption of valproic acid from some formulations (e.g., enteric‐coated) but not others (e.g., gelatine or sustained release; Hamilton et al, 1981; Fischer et al, 1988; Retzow et al, 1997). The Vd of valproic acid is 0.15–0.20 L/kg.…”

Section: Relevance Of Tdm For Individual Aedsmentioning

confidence: 99%

Antiepileptic drugs—best practice guidelines for therapeutic drug monitoring: A position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies

et al. 2008

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SUMMARYAlthough no randomized studies have demonstrated a positive impact of therapeutic drug monitoring (TDM) on clinical outcome in epilepsy, evidence from nonrandomized studies and everyday clinical experience does indicate that measuring serum concentrations of old and new generation antiepileptic drugs (AEDs) can have a valuable role in guiding patient management provided that concentrations are measured with a clear indication and are interpreted critically, taking into account the whole clinical context. Situations in which AED measurements are most likely to be of benefit include (1) when a person has attained the desired clinical outcome, to establish an individual therapeutic concentration which can be used at subsequent times to assess potential causes for a change in drug response; (2) as an aid in the diagnosis of clinical toxicity; (3) to assess compliance, particularly in patients with uncontrolled seizures or breakthrough seizures; (4) to guide dosage adjustment in situations associated with increased pharmacokinetic variability (e.g., children, the elderly, patients with associated diseases, drug formulation changes); (5) when a potentially important pharmacokinetic change is anticipated (e.g., in pregnancy, or when an interacting drug is added or removed); (6) to guide dose adjustments for AEDs with dose-dependent pharmacokinetics, particularly phenytoin.

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“…Finally, the serum concentration can be strongly influenced by combination with phenytoin (49.5%), carbamazepine (66.2%), or phenobarbital (76.3%) than when given alone (100%). On average, 250 mg VPA ingested induce a serum concentration of 54.6 ug/mL (0.34 mM) [ 32 ]. Overdosage of VPA results in somnolence, heart block or deep coma.…”

Section: Vpa Targets a Wide Range Of Pathologiesmentioning

confidence: 99%

Molecular and Therapeutic Potential and Toxicity of Valproic Acid

Chateauvieux

Morceau

Dicato

et al. 2010

Journal of Biomedicine and Biotechnology

379

308

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Valproic acid (VPA), a branched short-chain fatty acid, is widely used as an antiepileptic drug and a mood stabilizer. Antiepileptic properties have been attributed to inhibition of Gamma Amino Butyrate (GABA) transaminobutyrate and of ion channels. VPA was recently classified among the Histone Deacetylase Inhibitors, acting directly at the level of gene transcription by inhibiting histone deacetylation and making transcription sites more accessible. VPA is a widely used drug, particularly for children suffering from epilepsy. Due to the increasing number of clinical trials involving VPA, and interesting results obtained, this molecule will be implicated in an increasing number of therapies. However side effects of VPA are substantially described in the literature whereas they are poorly discussed in articles focusing on its therapeutic use. This paper aims to give an overview of the different clinical-trials involving VPA and its side effects encountered during treatment as well as its molecular properties.

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Effects of food on valproic acid absorption

Cited by 7 publications

References 0 publications

Using iPSC‐derived human DA neurons from opioid‐dependent subjects to study dopamine dynamics

Using iPSC‐derived human DA neurons from opioid‐dependent subjects to study dopamine dynamics

Antiepileptic drugs—best practice guidelines for therapeutic drug monitoring: A position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies

Molecular and Therapeutic Potential and Toxicity of Valproic Acid

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