ArticleNuclear medicine and biology2013
Whole-body pharmacokinetics of HDAC inhibitor drugs, butyric acid, valproic acid and 4-phenylbutyric acid measured with carbon-11 labeled analogs by PET.
Article in Nuclear medicine and biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
57 citing papers in PubMed, 101 citations in OpenAlex.
- Trial
- The Role of Sodium Valproate in Clozapine-Associated Cardiotoxicities: The Importance of Cellular and Systemic Energetics.Cardiovascular toxicology · 2026Review
- Review
- The Multifaceted Roles of Gut Microbiota and Their Metabolites in Metabolic Dysfunction-associated Steatotic Liver Disease: A Literature Review.Journal of clinical and translational hepatology · 2026Review
- HDAC inhibitors in cancer therapy: sensitization mechanisms, combination strategies, and translational challenges.Frontiers in cell and developmental biology · 2026Review
- Dietary tributyrin supplementation in Parkinson's disease: An open-label target engagement study.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- The Therapeutic Potential of Butyrate and Lauric Acid in Modulating Glial and Neuronal Activity in Alzheimer's Disease.Nutrients · 2025Review
- Gut commensaliScience · 2024Article
- The role of morphine- and fentanyl-induced impairment of intestinal epithelial antibacterial activity in dysbiosis and its impact on the microbiota-gut-brain axis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Brain Short-Chain Fatty Acids Induce ACSS2 to Ameliorate Depressive-Like Behavior via PPARγ-TPH2 Axis.Research (Washington, D.C.) · 2024Article
- Molecular mechanisms and therapeutic possibilities of short-chain fatty acids in posttraumatic stress disorder patients: a mini-review.Frontiers in neuroscience · 2024Review
- Chemical chaperon 4-phenylbutric acid improves cardiac function following isoproterenol-induced myocardial infarction in rats.Iranian journal of basic medical sciences · 2023Article
- Introducing HDAC-Targeting Radiopharmaceuticals for Glioblastoma Imaging and Therapy.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Radiosynthesis, Preclinical, and Clinical Positron Emission Tomography Studies of Carbon-11 Labeled Endogenous and Natural Exogenous Compounds.Chemical reviews · 2023Review
- Avenues within the gut-liver-brain axis linking chronic liver disease and symptoms.Frontiers in neuroscience · 2023Review
- Short-term effects of etifoxine on human gut microbiome in healthy men.Frontiers in neuroscience · 2023Article
- Butyrate and obesity: Current research status and future prospect.Frontiers in endocrinology · 2023Review
- Butyrate to combat obesity and obesity-associated metabolic disorders: Current status and future implications for therapeutic use.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2022Review
- A Role for Histone Deacetylases in the Biology and Treatment of Post-Traumatic Stress Disorder: What Do We Know and Where Do We Go from Here?Complex psychiatry · 2022Review
- Sodium butyrate reduces endoplasmic reticulum stress by modulating CHOP and empowers favorable anti-inflammatory adipose tissue immune-metabolism in HFD fed mice model of obesity.Food chemistry. Molecular sciences · 2022Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
Abstract
The fatty acids, n-butyric acid (BA), 4-phenylbutyric acid (PBA) and valproic acid (VPA, 2-propylpentanoic acid) have been used for many years in the treatment of a variety of CNS and peripheral organ diseases including cancer. New information that these drugs alter epigenetic processes through their inhibition of histone deacetylases (HDACs) has renewed interest in their biodistribution and pharmacokinetics and the relationship of these properties to their therapeutic and side effect profiles. In order to determine the pharmacokinetics and biodistribution of these drugs in primates, we synthesized their carbon-11 labeled analogues and performed dynamic positron emission tomography (PET) in six female baboons over 90 min. The carbon-11 labeled carboxylic acids were prepared by using (11)CO2 and the appropriate Grignard reagents. [(11)C]BA was metabolized rapidly (only 20% of the total carbon-11 in plasma was parent compound at 5 min post injection) whereas for VPA and PBA 98% and 85% of the radioactivity were the unmetabolized compound at 30 min after their administration respectively. The brain uptake of all three carboxylic acids was very low (<0.006%ID/cc, BA>VPA>PBA), which is consistent with the need for very high doses for therapeutic efficacy. Most of the radioactivity was excreted through the kidneys and accumulated in the bladder. However, the organ biodistribution between the drugs differed. [(11)C]BA showed relatively high uptake in spleen and pancreas whereas [(11)C]PBA showed high uptake in liver and heart. Notably, [(11)C]VPA showed exceptionally high heart uptake possibly due to its involvement in lipid metabolism. The unique biodistribution of each of these drugs may be of relevance in understanding their therapeutic and side effect profile including their teratogenic effects.
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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.