Dichloroacetate Kinetics, Metabolism and Toxicology
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)
Links
- Source: http://clinicaltrials.gov/show/NCT00015015
- Information obtained from ClinicalTrials.gov on July 15, 2010
Published on BioPortfolio: 2014-07-24T14:35:04-0400
Clinical Trials
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).
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...
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...
Glucose-insulin-potassium Therapy Improves Lactic Acidosis in Liver Transplantation
Lactic acidosis is a common phenomenon occurring during orthotopic liver transplantation (OLT), especially during the anhepatic and early postreperfusion phases. However, little drugs effe...
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...
PubMed Articles
Lactic Acidosis in a Critically Ill Patient: Not Always Sepsis.
Lactic acidosis in the emergency department and other hospital settings is typically due to tissue hypoxia with sepsis being the most common cause. However, in patients with persistently elevated lact...
Severe lactic acidosis in an extremely low birth weight infant due to thiamine deficiency.
In this case report, we present a preterm newborn with persistent lactic acidosis who received total parenteral nutrition (TPN) that lacked thiamine.
Risk of lactic acidosis in type 2 diabetes patients using metformin: A case control study.
Metformin constitutes first-line treatment of type 2 diabetes mellitus. It is presumed to have lactic acidosis as a dangerous, but rare, side effect.
Fatal lactic acidosis has been reported while on the treatment with Nucleoside/nucleotide analogs (NA) for the treatment of hepatitis B, C and HIV. No cases of such a complication have been reported i...
Pharmaceutical preformulation studies and paediatric oral formulations of sodium dichloroacetate.
The purpose of this study was to develop liquid and solid paediatric formulations of sodium dichloroacetate (DCA) for the treatment of congenital lactic acidosis (CLA). In this work preformulation stu...
Medical and Biotech [MESH] Definitions
Acidosis, Lactic
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.
Hyperlactatemia
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.
Pyruvate Dehydrogenase Complex Deficiency Disease
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.
Shock, Septic
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.
Phenformin
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)
