Pharmacotoxicology of Trichloroethylene Metabolites:
To establish the relationship between human MAAI haplotype and DCA and tyrosine metabolism. This aim test the postulates that MAAI haplotype determines, and thus can predict,1) dose-dependent DCA kinetics and biotransformation and 2) DCA's effects on tyrosine metabolism.
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
|Official Title:||Pharmacotoxicology of Trichloroethylene Metabolites|
- Hypothesize that subject's genotype will determine how DCA is metabolized [ Time Frame: August, 2009 - November 2012 ] [ Designated as safety issue: No ]
|Study Start Date:||August 2009|
|Estimated Study Completion Date:||November 2012|
|Estimated Primary Completion Date:||November 2012 (Final data collection date for primary outcome measure)|
Experimental: DCA 2.5.ug/kg
Dichloroacetate 2.5ug/kg /day is administered for five days.
Drug: Dichloroacetate 2.5.ug/kg
Subjects are admitted to the clinical research center for 6 nights. The first day subjects are administer 2.5ug/kg/day. Frequent blood samples are collected over a 24 hour period. On days 2,3,4 subjects receive a dose of DCA each day. On day 5 they receive a dose of DCA and pharmacokinetics are done for 24 hours then subjects are discharged.
Experimental: 'DCA 25mg/kg Clinical Dose'
25mg/kg of dichloroacetate (DCA) was given 30 days after low dose DCA. Clinical dose was given for five days.
Drug: DCA 25mg/kg Clinical Dose
Subjects are admitted to the clinical research center Thirty days after the 2.5ug/kg dose. Subjects receive 25mg/kg/ day of DCA. On day 1 pharmacokinetics are done for 24hours. Days 2,3,4 subjects receive a dose of DCA. On day 5 subjects receive a dose of DCA and have pharmacokinetics for 24 hours and are then discharged home.
The arms of the study involves an admission to the clinical research center. There participants will first take a low dose of DCA 2.5ug/kg for 5 days then wait 30 days and take a therapeutic dose of DCA 25mg/kg for 5 days On the first day and on the 5th day of taking DCA kinetics will be done. A total of 16 blood samples will be obtained through an intravenous catheter. Subjects will also breath into a test tube for the collection of CO2. Urine collection will also occur
|United States, Florida|
|University of Florida Shands Hospital|
|Gainesville, Florida, United States, 32610|
|Principal Investigator:||Peter W Stacpoole, PhD, MD||University of Florida|