ReviewExpert opinion on drug metabolism & toxicology2017
An update on the use of benzoate, phenylacetate and phenylbutyrate ammonia scavengers for interrogating and modifying liver nitrogen metabolism and its implications in urea cycle disorders and liver disease.
Review in Expert opinion on drug metabolism & toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Pharmacotherapies that specifically target ammonia for the prevention and treatment of hepatic encephalopathy in adults with cirrhosis.The Cochrane database of systematic reviews · 2019Pooled it
- Optimising Formulations for Paediatric Patients with Inherited Metabolic Disorders: The Case Study of Levocarnitine.Pharmaceutical medicine · 2026Review
- Pre-emptive treatment in later-onset urea cycle disorders: a clinical perspective on glycerol phenylbutyrate.Orphanet journal of rare diseases · 2026Review
- Research progress and therapeutic strategies in hepatocellular carcinoma metabolic reprogramming.Journal of advanced research · 2026Review
- Targeted Hepatic Delivery of Bioactive Molecules via Nanovesicles: Recent Developments and Emerging Directions.Journal of personalized medicine · 2025Review
- Article
- Characterization of a novel conditional knockout mouse model to assess efficacy of mRNA therapy in the context of severe OTC deficiency.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- My path to citrin deficiency.Journal of inherited metabolic disease · 2025Review
- The therapeutic landscape of citrin deficiency.Journal of inherited metabolic disease · 2024Review
- Treatment of Hyperammonemia Syndrome in Lung Transplant Recipients.Journal of clinical medicine · 2023Review
- Lysinuric Protein Intolerance and Its Nutritional and Multisystemic Challenges in Pregnancy: A Case Report and Literature Review.Journal of clinical medicine · 2023Review
- Lipid nanoparticle-targeted mRNA formulation as a treatment for ornithine-transcarbamylase deficiency model mice.Molecular therapy. Nucleic acids · 2023Article
- Article
- Topical phenylbutyrate antagonizes NF-κB signaling and resolves corneal inflammation.iScience · 2022Article
- Effect of storage on the levels of sodium benzoate in soft drinks sold in some Nigerian market with exposure and health risk assessment.Environmental analysis, health and toxicology · 2022Article
- Switching to Glycerol Phenylbutyrate in 48 Patients with Urea Cycle Disorders: Clinical Experience in Spain.Journal of clinical medicine · 2022Article
- Toxic Metabolites and Inborn Errors of Amino Acid Metabolism: What One Informs about the Other.Metabolites · 2022Review
- The effect of sodium benzoate, L-carnitine, and phenylacetate on valproate-induced hyperammonemia in Male Wistar rats.International journal of physiology, pathophysiology and pharmacology · 2022Article
- Sodium Benzoate Delays the Development ofFrontiers in microbiology · 2022Article
- Humanized liver mouse model with transplanted human hepatocytes from patients with ornithine transcarbamylase deficiency.Journal of inherited metabolic disease · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
introductionAmmonia-scavenging drugs, benzoate and phenylacetate (PA)/phenylbutyrate (PB), modulate hepatic nitrogen metabolism mainly by providing alternative pathways for nitrogen disposal. Areas covered: We review the major findings and potential novel applications of ammonia-scavenging drugs, focusing on urea cycle disorders and liver disease. Expert opinion: For over 40 years, ammonia-scavenging drugs have been used in the treatment of urea cycle disorders. Recently, the use of these compounds has been advocated in acute liver failure and cirrhosis for reducing hyperammonemic-induced hepatic encephalopathy. The efficacy and mechanisms underlying the antitumor effects of these ammonia-scavenging drugs in liver cancer are more controversial and are discussed in the review. Overall, as ammonia-scavenging drugs are usually safe and well tolerated among cancer patients, further studies should be instigated to explore the role of these drugs in liver cancer. Considering the relevance of glutamine metabolism to the progression and resolution of liver disease, we propose that ammonia-scavenging drugs might also be used to non-invasively probe liver glutamine metabolism in vivo. Finally, novel derivatives of classical ammonia-scavenging drugs with fewer and less severe adverse effects are currently being developed and used in clinical trials for the treatment of acute liver failure and cirrhosis.
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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.