Trial reportClinical pharmacokinetics2018
Safety and Tolerability of Intravenous Valproic Acid in Healthy Subjects: A Phase I Dose-Escalation Trial.
Trial report in Clinical pharmacokinetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 32 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1, Single Ascending Dose, Double Blind, Placebo Controlled Study to Evaluate the Safety and Tolerability of Valproic Acid in Healthy Volunteers (Part 1) or Trauma Patients(Part 2)
Evaluation of Valproic Acid (VPA) as Adjunctive Therapy for Trauma Patients With Moderate to Severe Hemorrhage at Risk of Ischemia Reperfusion (I/R) Injury
Evaluation of Valproic Acid (VPA) as Adjunctive Therapy for Liver Transplant Patients With Moderate to Severe Hemorrhage at Risk of Ischemia Reperfusion (I/R) Injury
Who cites it
32 citing papers in PubMed, 4 syntheses or guidelines pooled it, 52 citations in OpenAlex.
- Practice advisory for intravenous management of headache disorders in hospitalized patients: a review of the evidence and consensus recommendations.Regional anesthesia and pain medicine · 2026Pooled it
- Adjuvant therapies for management of hemorrhagic shock: a narrative review.Critical care (London, England) · 2025Pooled it
- Epigenetic mechanisms of Immune remodeling in sepsis: targeting histone modification.Cell death & disease · 2023Pooled it
- Association of Valproic Acid Use With Post-Myocardial Infarction Heart Failure Development: A Meta-Analysis of Two Retrospective Case-Control Studies.Journal of cardiovascular pharmacology and therapeuticsPooled it
- Valproic acid for treatment of traumatic brain injury: Study protocol for the VIBRANT prospective randomized trial.Transfusion · 2026Article
- Quantitative systems toxicology approach that integrates PBPK and core hepatic metabolism: a case study with valproic acid.Frontiers in pharmacology · 2026Article
- Harnessing Electrophiles In Vivo: A Pilot Study in Swine Using a Hydrophobic Radiopaque Formulation of 2-Propylpentanoyl Chloride.Molecular pharmaceutics · 2025Article
- Physiologically-Based Pharmacokinetic Modeling of Total and Unbound Valproic Acid to Evaluate Dosing in Children With and Without Hypoalbuminemia.Clinical pharmacokinetics · 2024Article
- Article
- Anti-seizure Medications: Challenges and Opportunities.CNS & neurological disorders drug targets · 2024Review
- Role of the immune system in liver transplantation and its implications for therapeutic interventions.MedComm · 2023Review
- A comprehensive review on pharmacological applications and drug-induced toxicity of valproic acid.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Review
- Assessment of porphyrogenicity of drugs and chemicals in selected hepatic cell culture models through a fluorescence-based screening assay.Pharmacology research & perspectives · 2022Article
- Valproic Acid Protects Against Acute Kidney Injury in Hemorrhage and Trauma.The Journal of surgical research · 2021Article
- The Effect of Plasma Protein Binding on the Therapeutic Monitoring of Antiseizure Medications.Pharmaceutics · 2021Review
- Resuscitative endovascular balloon occlusion of the aorta in combat casualties: The past, present, and future.The journal of trauma and acute care surgery · 2021Review
- Differential molecular response of larynx cancer cell lines to combined VPA/CDDP treatment.American journal of cancer research · 2021Article
- Brain proteomic changes by histone deacetylase inhibition after traumatic brain injury.Trauma surgery & acute care open · 2021Article
- Epigenetic Regulation in Sepsis, Role in Pathophysiology and Therapeutic Perspective.Frontiers in medicine · 2021Review
- Valproic acid treatment rescues injured tissues after traumatic brain injury.The journal of trauma and acute care surgery · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
backgroundValproic acid, a histone deacetylase inhibitor, has beneficial effects in the setting of cancer, neurologic diseases, and traumatic injuries. In animal models of traumatic injury, a single dose of valproic acid has been shown to reduce mortality. The purpose of this trial was to determine the maximum tolerated single dose of intravenous valproic acid in healthy humans.
methodsA double-blinded, placebo-controlled, dose-escalation trial design was used to identify dose-limiting toxicities in healthy subjects who received a single dose of intravenous valproic acid. Patients were monitored for adverse events and data were collected for pharmacokinetic, pharmacodynamic, and safety profiling of valproic acid.
resultsFifty-nine healthy subjects (mean 30 ± 12 years) were enrolled. Forty-four subjects received valproic acid in doses from 15 to 150 mg/kg. The most common adverse events were hypoacusis (n = 19), chills (n = 18), and headache (n = 16). The maximum tolerated dose was 140 mg/kg. Dose-limiting toxicities included headache and nausea lasting longer than 12 h. No drug-related abnormalities were seen in other safety measures including laboratory tests, hemodynamic parameters, cardiac rhythm monitoring, and cognitive testing. A two-compartment model was predictive of valproic acid concentration-time profiles, with a strong correlation (R
conclusionsThe maximum tolerated dose of intravenous valproic acid in healthy subjects is 140 mg/kg. This is significantly higher than the previously established maximum tolerated dose of 60-75 mg/kg. Next, the safety and tolerability of high-dose valproic acid will be tested in trauma patients in hemorrhagic shock. ClinicalTrials.gov Identifier: NCT01951560.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.