Trial reportJournal of clinical pharmacology2015
Haplotype variations in glutathione transferase zeta 1 influence the kinetics and dynamics of chronic dichloroacetate in children.
Trial report in Journal of clinical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02616484 (Phase 3 Trial of Dichloroacetate in Pyruvate Dehydrogenase Complex Deficiency), which is not on this map. Cited by 13 papers.
What it found
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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.
Phase 3 Trial of Dichloroacetate in Pyruvate Dehydrogenase Complex Deficiency:
Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Model Informed Dose Optimization of Dichloroacetate for the Treatment of Congenital Lactic Acidosis in Children.Journal of clinical pharmacology · 2018Trial
- Chloral hydrate, through biotransformation to dichloroacetate, inhibits maleylacetoacetate isomerase and tyrosine catabolism in humans.Drug metabolism and personalized therapy · 2015Trial
- Mitochondria-Targeted Nanotherapies in Aging Neurodegenerative Disorders: Emerging Prospects and Clinical Potential.Advanced healthcare materials · 2026Review
- Neuroprotective Effects and Therapeutic Potential of Dichloroacetate: Targeting Metabolic Disorders in Nervous System Diseases.International journal of nanomedicine · 2023Review
- Dichloroacetate and PX-478 exhibit strong synergistic effects in a various number of cancer cell lines.BMC cancer · 2021Article
- Pharmacokinetic and Biochemical Profiling of Sodium Dichloroacetate in Pregnant Ewes and Fetuses.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- GlutathioneDrug design, development and therapy · 2018Review
- Therapeutic applications of dichloroacetate and the role of glutathione transferase zeta-1.Pharmacology & therapeutics · 2017Review
- Pharmacogenetic considerations with dichloroacetate dosing.Pharmacogenomics · 2016Review
- The Genetic Architecture of Murine Glutathione Transferases.PloS one · 2016Article
- The influence of human GSTZ1 gene haplotype variations on GSTZ1 expression.Pharmacogenetics and genomics · 2015Article
- Chloride concentrations in human hepatic cytosol and mitochondria are a function of age.Biochemical and biophysical research communications · 2015Article
- Interactome analysis of gene expression profile reveals potential novel key transcriptional regulators of skin pathology in vitiligo.Genes and immunityArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Dichloroacetate (DCA) is biotransformed by glutathione transferase zeta 1 (GSTZ1), a bifunctional enzyme that, as maleylacetoacetate isomerase (MAAI), catalyzes the penultimate step in tyrosine catabolism. DCA inhibits GSTZ1/MAAI, leading to delayed plasma drug clearance and to accumulation of potentially toxic tyrosine intermediates. Haplotype variability in GSTZ1 influences short-term DCA kinetics in healthy adults, but the impact of genotype in children treated chronically with DCA is unknown. Drug kinetics was studied in 17 children and adolescents with congenital mitochondrial diseases administered 1,2-(13) C-DCA. Plasma drug half-life and trough levels varied 3-6-fold, depending on GSTZ1/MAAI haplotype and correlated directly with urinary maleylacetone, a substrate for MAAI. However, chronic DCA exposure did not lead to progressive accumulation of plasma drug concentration; instead, kinetics parameters plateaued, consistent with the hypothesis that equipoise is established between the inhibitory effect of DCA on GSTZ1/MAAI and new enzyme synthesis. GSTZ1/MAAI haplotype variability affects DCA kinetics and biotransformation. However, these differences appear to be stable in most individuals and are not associated with DCA plasma accumulation or drug-associated toxicity in young children.
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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.