Comparative bioavailaibilty of two valproic acid delayed-release tablets in healthy volunteers with tighter acceptance criteria to anticipate breakthrough seizures (original) (raw)
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Revista de investigación clínica; organo del Hospital de Enfermedades de la Nutrición
Most of bayesian pharmacokinetic studies and the influence of clinical variables have been carried out in adults. The aim was to estimate population-based pharmacokinetic of valproic acid (VPA) and to determine the effect of treatment and additional disease on its performance in children with epilepsy. For the study steady-state serum concentrations of VPA were determined from 108 epileptic patients (44 females and 64 males) who were receiving the anticonvulsant as main drug of treatment with age range since 1 to 16 years (median 4y, 6m) and weight since 5.2 to 50 kg (median 17.5 kg). All patients had their renal, hepatic and nutritional functions normal. One compartment model using interactive two-stage Bayesian approach was employed in the analysis. RESULTS; Population estimates of CL/F and V/F for VPA were 0.022 +/- 0.013 L/h and 0.217 +/- 0.134 L/kg, respectively. These estimates were significantly affected by weight, age, carbamazepine (CBZ) and gastroesophageal reflux (GER). T...
European Journal of Clinical Pharmacology, 2006
Conventional and sustained-release valproate in children with newly diagnosed epilepsy: a randomized and crossover study comparing clinical effects, patient preference and pharmacokinetics Abstract Objective: It has been suggested that sustainedrelease valproate (VPA) formulations may be more effective and better tolerated than conventional VPA due to better compliance and lower fluctuations in VPA serum concentrations, but comparative trials with conventional VPA in children are scarce. This randomized and crossover trial compared the efficacy (complete control of seizures), the tolerability, and the patient (or parents) preference of conventional VPA twice daily (CVbid) with those of sustained-release chrono VPA twice daily (ChVbid), once daily in the morning (ChVom) or once daily in the evening (ChVoe) in monotherapy. Methods: The study was carried out in 48 children (29 girls), aged 5-14 years, with newly diagnosed partial epilepsy (n=26), or idiopathic generalized epilepsy (n=22). The study duration was 16 months (four phases of 4 months each). VPA pharmacokinetics data were also compared in the different regimens. Mean VPA dosage was of approximately 870 mg/day (approximately 22 mg/kg/day) and mean VPA concentration was of approximately 89 mg/l at 12 h post-dose and of 54 mg/l at 24 h post-dose. Results: By intention in treatment there were no significant differences in efficacy (73%, 83%, 77% and 75%, respectively) or in adverse reaction frequency (56%, 58%, 67% and 46%, respectively). There were significant differences, however, in patient (or parents) preference, the order being ChVoe (31%) > ChVom (25%) > CVbid (17%) > ChVbid (8%). The mean VPA serum concentration fluctuation between 4 h and 0 h post-morning-dose was nonsignificantly lower after CVbid than after ChVbid. Fluctuation was significantly higher after ChVom than after CVbid or ChVbid. The mean VPA serum concentration difference between 12 h and 24 h post-dose was approximately 40 mg/l. Conclusion: Although our results should be confirmed by a larger study, they suggest that the efficacy and tolerability of chrono valproate is similar to that of conventional valproate, and that the main advantage is the once-daily administration.
Saudi medical journal, 2007
To evaluate the efficacy and safety of valproate (VPA) sustained-released in monotherapy across all ages in newly-diagnosed epileptic patients with partial seizures (PS) with or without secondary generalization. This was a multicenter, prospective, observational, open-label, non-comparative study involving the Gulf Cooperation Council (GCC) countries except the Kingdom of Saudi Arabia, and was performed between November 2004 and May 2006. Adults and children (6 years or older with newly diagnosed partial epilepsy [PE]) with or without secondary generalization were enrolled. The primary efficacy parameter was 6 month-remission rate (proportion of seizure-free patients in relation to total number of retained patients). Secondary efficacy parameters included: 6 month-retention rate, investigator's clinical global impression rating, maximal effective dose and safety profile. Seventy-seven patients were enrolled; 56% adults and 44% children, with average duration of epilepsy of 5 mon...
2007
Objective: To evaluate the efficacy and safety of valproate (VPA) sustainedreleased in monotherapy across all ages in newly-diagnosed epileptic patients with partial seizures (PS) with or without secondary generalization. Methods: This was a multicenter, prospective, observational, open-label, noncomparative study involving the Gulf Cooperation Council (GCC) countries except the Kingdom of Saudi Arabia, and was performed between November 2004 and May 2006. Adults and children (6 years or older with newly diagnosed partial epilepsy [PE]) with or without secondary generalization were enrolled. The primary efficacy parameter was 6 month-remission rate (proportion of seizure-free patients in relation to total number of retained patients). Secondary efficacy parameters included: 6 month-retention rate, investigator’s clinical global impression rating, maximal effective dose and safety profile. Results: Seventy-seven patients were enrolled; 56% adults and 44% children, with average durati...
Factors Associated with Good Seizure Control in Patients on Valproic Acid
The Eurasian Journal of Medicine
Aims and Scope Eurasian Journal of Medicine (Eurasian J Med) is an international, scientific, open access periodical published by independent, unbiased, and triple-blinded peer-review principles. The journal is the official publication of Atatürk University School of Medicine and published triannually in February, June, and October. The publication language of the journal is English. The aim of the Eurasian Journal of Medicine is to publish original research papers of the highest scientific and clinical value in all medical fields. The Eurasian J Med also includes reviews, editorial short notes and letters to the editor that either as a comment related to recently published articles in our journal or as a case report. The target audience of the journal includes researchers, physicians and healthcare professionals who are interested or working in in all medical disciplines.
Serum concentrations of valproic acid in people with epilepsy: Clinical implication
Journal of Pharmacy & Pharmacognosy Research, 2022
Context: Therapeutic drug monitoring (TDM) allows personalizing the dose of valproic acid in patients with epilepsy to optimize drug therapy, minimize adverse effects and detect interactions. Aims: To determine valproic acid concentrations in serum samples from people with epilepsy and to analyze its clinical implications. Methods: Cloned donor enzyme immunoassay; descriptive, cross-sectional, non-randomized, convenience recruitment study of 57 voluntary patients with epilepsy (n = 39 male, 68.42%; n = 18 female, 31.58%) aged between 19 and 62 years. After three months of treatment with valproic acid, a single blood sample was collected from each volunteer at a minimal concentration. Results: Serum drug concentrations 51.30-100.10 mg/L (SD 5.94) and level/dose 2.17-5.31 (SD 1.14) were observed. Association was shown between the dose ratio/dose of valproic acid (R 2 = 0.8693; p<0.05) and the Mann-Whitney U test (p<0.05). Valproic acid monotherapy and association with carbamazepine and phenytoin are not different between treatment groups (Mann-Whitney U test: p = 0.391 > α = 0.05). Conclusions: Serum valproic acid concentrations are within the therapeutic range, and there is a significant inverse linear correlation between dose ratio/dose, which must be considered to personalize the dose and optimize the pharmacotherapeutic result.
Disposition of sodium valproate in epileptic patients
British Journal of Clinical Pharmacology, 1978
I Serum levels of valproic acid have been determined at fixed intervals after the administration of single oral and intravenous doses (800 mg) to six epileptic patients receiving chronic treatment with other antiepileptic drugs. 2 Serum levels declined monoexponentially shortly after the intravenous administration. Biological half-lives averaged 9.0-±1.4 h (s.d.). Volumes of distribution were 0.175 ± 0.025 1/kg. There was a statistically significant negative correlation between volumes of distribution and serum half-lives (P < 0.005). 3 After oral doses serum levels rose rapidly to peak values within 0.5-2 h. Biological availability was 96 + 9%. 4 Comparison with a previous study performed according to the same protocol in healthy volunteers showed significantly increased volumes of distribution and rates of elimination in the patients. Total serum clearance was 85% higher in the patients as compared to the healthy subjects (P <0.001). Possible explanations for these findings are discussed.