Actual bioavailability of divalproex sodium extended-release tablets and its clinical implications

Fagiolino, Pietro; Martín, Omar; Gónzalez, Nicolás; Malanga, Antonio

doi:10.1590/s1676-26492007000200007

Cited by 3 publications

(1 citation statement)

References 6 publications

(8 reference statements)

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“…Patients receiving VPA-ER had fewer central nervous system adverse effects (i.e., fatigue/asthenia, headache, memory loss, and tremor), weight increase, and hair alterations. At present, a large number of pharmacokinetic studies have shown that the significantly decreased peak-trough fluctuation of plasma valproic acid levels and the stable serum concentrations of divalproex contribute to preventing concentration-dependent AEs ( Ieiri et al, 1995 ; Kondo et al, 2002 ; Smith et al, 2004 ; Fagiolino et al, 2007 ), such as central AEs. Nevertheless, the specific reasons for this need to be further explored.…”

Section: Discussionmentioning

confidence: 99%

Efficacy, Safety, and Retention Rate of Extended-Release Divalproex Versus Conventional Delayed-Release Divalproex: A Meta-Analysis of Controlled Clinical Trials

Zhang¹,

Li²,

Wan³

et al. 2022

Front. Pharmacol.

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Purpose: A novel once-daily divalproex-extended release (ER) dose formulation has been developed; this formulation prolongs the therapeutic serum levels of the drug, compared with the twice-daily conventional divalproex-delayed release (DR) formulation. This study aimed to systematically examine and compare the efficacy, safety, and retention rates of the ER divalproex (VPA-ER) and conventional DR divalproex (VPA-DR) formulations.Methods: Randomized control trials (RCTs) reporting the efficacy, adverse events (AEs), and medication compliance of ER and DR divalproex were searched in online databases, including PubMed, Embase, and Cochrane Library databases, by searching MeSH words and term words. Observational studies with potential biases were excluded. The meta-analysis was performed using Stata 16.0 software.Findings: Thirteen RCTs, involving 1,028 participants, were included in this meta-analysis. Efficacy, AEs, and drug retention rates were the main study outcomes. According to our study, VPA-ER presented clinically significant benefits compared with the placebo in the population with bipolar disorder (BD) (39.5% versus 27.2%, p < 0.001). A similar efficacy of VPA-ER and VPA-DR in controlling seizures was observed in epilepsy patients (87.4% versus 86.5%, p = 0.769). A significantly lower incidence of AEs was reported in the VPA-ER group than in the placebo group (26.8% versus 34.8%, p = 0.003). By contrast, there was no evidence of difference in safety between VPA-ER and VPA-DR (29.4% versus 30.5%, p = 0.750). In addition, the drug retention rate was significantly lower in the VPA-ER group than in the placebo group (76.0% versus 82.7%, p = 0.020), especially in migraine patients (p = 0.022) and in patients who were treated for fewer than 4 weeks (p = 0.018).Implications: The efficacy of VPA-ER was significantly superior to that of the placebo treatment, which provided efficacy similar to that of conventional VPA-DR. VPA-ER is well tolerated with a low rate of AEs compared to the placebo. In addition, the acceptable medicine compliance of VPA-ER was conducive to the long-term maintenance treatment of chronic diseases. Although we analyzed open labels and crossover design RCTs, large-scale multicenter studies on the efficacy and medicine compliance of new ER formulations with less AEs are required to validate our conclusion.

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Section: Discussionmentioning

confidence: 99%

Efficacy, Safety, and Retention Rate of Extended-Release Divalproex Versus Conventional Delayed-Release Divalproex: A Meta-Analysis of Controlled Clinical Trials

Zhang¹,

Li²,

Wan³

et al. 2022

Front. Pharmacol.

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Contribution of the Antiepileptic Drug Administration Regime in the Development and/or Establishment of Pharmacoresistant Epilepsy

Fagiolino

Vázquez

Orozco‐Suárez³

et al. 2013

Pharmacoresistance in Epilepsy

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Antiepileptic drugs Energy-consuming processes governing drug disposition

et al. 2014

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Diffusion is not the main process by which drugs are disposed throughout the body. Translational movements of solutes given by different energy-consuming mechanisms are required in order to dispose them efficiently. Membrane transportation and cardiac output distribution are two effective processes to move the molecules among different body sites. Gastrointestinal-blood cycling constitutes a supplementary way to regulate the distribution of molecules between the non-hepatic organs and the liver. Any change in the relative supply of drug molecules among eliminating organs could modify their clearance from the body. Either the nonlinear phenytoin (PHT) pharmacokinetic response or the influence that carbamazepine (CBZ) exerts on PHT exposure could be explained throughout their efflux transporter inducer abilities. Cardiac output distribution difference between the individuals might also explain the dual CBZ-over-PHT interaction response. Finally, valproic acid (VPA) pharmacokinetics can be understood by adding to these mechanisms of transportation its ability to cross the mitochondrial membrane of the hepatocyte.

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Actual bioavailability of divalproex sodium extended-release tablets and its clinical implications

Cited by 3 publications

References 6 publications

Efficacy, Safety, and Retention Rate of Extended-Release Divalproex Versus Conventional Delayed-Release Divalproex: A Meta-Analysis of Controlled Clinical Trials

Efficacy, Safety, and Retention Rate of Extended-Release Divalproex Versus Conventional Delayed-Release Divalproex: A Meta-Analysis of Controlled Clinical Trials

Contribution of the Antiepileptic Drug Administration Regime in the Development and/or Establishment of Pharmacoresistant Epilepsy

Antiepileptic drugs Energy-consuming processes governing drug disposition

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