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Dichloroacetate Kinetics, Metabolism and Toxicology

2014-07-24 14:35:04 | BioPortfolio

Summary

Dichloroacetate (DCA) is a product of water chlorination and a metabolite of certain industrial solvents, thus making it a chemical of environmental concern. However, DCA is also used as an investigational drug for treating various diseases of adults and children, at doses far greater than those to which humans are normally exposed in the environment. Our research involves how DCA is metabolized by healthy adults and by children with a fatal genetic disease, congenital lactic acidosis (CLA) who are treated with DCA.

Study Design

Observational Model: Defined Population, Primary Purpose: Screening, Time Perspective: Longitudinal, Time Perspective: Prospective

Conditions

Lactic Acidosis

Intervention

Dichloroacetate

Location

Univ. of Florida
Gainesville
Florida
United States
32610

Status

Completed

Source

National Institute of Environmental Health Sciences (NIEHS)

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-07-24T14:35:04-0400

Clinical Trials [127 Associated Clinical Trials listed on BioPortfolio]

Prevention of Dichloroacetate Toxicity

This is a study to determine the safety of dichloroacetate (DCA) with a low-tyrosine diet given with or without nitisinone (NTBC) in children with chronic lactic acidosis (CLA).

Phase II Pilot Randomized Study of Sodium Dichloroacetate in Patients With Congenital Lactic Acidemia

OBJECTIVES: I. Determine the pharmacokinetics of sodium dichloroacetate (DCA) in patients with congenital lactic acidemia. II. Determine the efficacy of DCA in decreasing the frequency a...

Study On the Role of Mitochondrial Dysfunction in the Pathogenesis of Metformin-associated Lactic Acidosis

Metformin is the first line drug of choice for the treatment of type II diabetes. Lactic acidosis can develop as a side effect, especially when renal failure leads to drug accumulation. La...

Trial of Dichloroacetate in Pyruvate Dehydrogenase Complex Deficiency:

The objective of this research study is to conduct a pivotal phase 3 trial of treatment with the investigational drug dichloroacetate (DCA) in young children with deficiency of the pyruvat...

A Phase I, Open-Labeled, Single-Arm, Dose Escalation, Clinical and Pharmacology Study of Dichloroacetate (DCA) in Patients With Recurrent and/or Metastatic Solid Tumours

Dichloroacetate (DCA) is a small molecule that has been used for years to treat lactic acidosis and rare metabolic disorders in humans. Further testing now shows that it may suppress the ...

PubMed Articles [475 Associated PubMed Articles listed on BioPortfolio]

Metformin-Induced Lactic Acidosis: A Case Study.

Metformin is the first line management for patients with Type 2 diabetes mellitus. Metformin-induced lactic acidosis (MALA) is a severe side effect of metformin in high doses. However, there have no...

Comparative analysis of lactic acidosis induced by linezolid and vancomycin therapy using cohort and case-control studies of incidence and associated risk factors.

Lactic acidosis is a rare complication of linezolid (LZD) therapy, and its incidence and risk factors remain unknown. This study aimed to compare the incidence of LZD-associated lactic acidosis (LALA)...

Severe lactic acidosis requiring continuos haemodiafiltration in a young patient with unrecognized metabolic abnormality. Case report.

Lactic acidosis (LA) is the most common form of metabolic acidosis, defined by lactate values greater than 5 mmol/L and pH

Combined metformin-associated lactic acidosis and euglycemic ketoacidosis.

In renal failure metformin can lead to lactic acidosis. Additional inhibition of hepatic gluconeogenesis by accumulation of the drug may aggravate fasting-induced ketoacidosis. We report the occurrenc...

Metformin-associated lactic acidosis. Report of one case.

Metformin-associated lactic acidosis is a severe and infrequent adverse event. Early diagnosis is essential to start an early treatment, which often has favorable results. We report a 56 years old non...

Medical and Biotech [MESH] Definitions

Acidosis caused by accumulation of lactic acid more rapidly than it can be metabolized. It may occur spontaneously or in association with diseases such as diabetes mellitus, leukemia, or liver failure.

Increase in blood LACTATE concentration often associated with SEPTIC SHOCK; LUNG INJURY; SEPSIS; and DRUG TOXICITY. When hyperlactatemia is associated with low body pH (acidosis) it is LACTIC ACIDOSIS.

An inherited metabolic disorder caused by deficient enzyme activity in the PYRUVATE DEHYDROGENASE COMPLEX, resulting in deficiency of acetyl CoA and reduced synthesis of acetylcholine. Two clinical forms are recognized: neonatal and juvenile. The neonatal form is a relatively common cause of lactic acidosis in the first weeks of life and may also feature an erythematous rash. The juvenile form presents with lactic acidosis, alopecia, intermittent ATAXIA; SEIZURES; and an erythematous rash. (From J Inherit Metab Dis 1996;19(4):452-62) Autosomal recessive and X-linked forms are caused by mutations in the genes for the three different enzyme components of this multisubunit pyruvate dehydrogenase complex. One of the mutations at Xp22.2-p22.1 in the gene for the E1 alpha component of the complex leads to LEIGH DISEASE.

Sepsis associated with HYPOTENSION or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include, but are not limited to LACTIC ACIDOSIS; OLIGURIA; or acute alteration in mental status.

A biguanide hypoglycemic agent with actions and uses similar to those of METFORMIN. Although it is generally considered to be associated with an unacceptably high incidence of lactic acidosis, often fatal, it is still available in some countries. (From Martindale, The Extra Pharmacopoeia, 30th ed, p290)

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