Pharmacotoxicology of Trichloroethylene Metabolites

Phase 1

Completed

Interventions: Drug: Dichloroacetate environmental dose
Drug: Dichloroacetate therapeutic dose
Drug: Chloral Hydrate therapeutic dose
Drug: Chloral Hydrate environmental dose

Brief Summary: This is a research study to look at how Dichloroacetate (DCA), and investigational drug and chloral hydrate are broken down in the body. The purpose of the study is to better understand how humans metabolize these two common chemicals that are widely present in the environment. The study focuses on how the drug chloral hydrate is broken down and how it effects DCA

Detailed Description: The subject's general health is assessed by a history and physical exam and routine blood work. I normal the individual undergoes five nights of receiving 1.5ug/kg of chloral hydrate. On day 6 the individual receives 2.5 micrograms/kg of Dichloroacetate (DCA) and kinetics are drawn. After 30 days the subject comes back and receives 1.5ug/kg of chloral hydrate for five nights and has kinetics drawn on night one and five. On days 6-9 the subject returns for a blood draw. After 30 days the same process as above is done except the subject receives 1gram of chloral hydrate for five nights and 25mg/kg of Dichloroacetate one day then 30 days later the subject receives 1gram of chloral hydrate for five nights and has kinetics done on night one and five and blood samples drawn on days 6-9

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

Arm && Interventions

Group	Intervention	Description
1A: Chloral Hydrate and DCA: Env	Dichloroacetate environmental dose	Subjects consume Chloral Hydrate 1.5ug/kg by mouth for 5 nights. On the 6th day they consume DCA 2.5ug/kg by mouth and have blood samples drawn. (Period 1)
2A: Chloral Hydrate and DCA therapeutic	Dichloroacetate therapeutic dose	Drug Study Subjects are admitted to the clinical research center and receive a clinical dose of Chloral Hydrate for 5 nights (25mg/kg). On day 6 they are given a clinical dose (25mg/kg)of Dichloroacetate. (Period 3)
2A: Chloral Hydrate and DCA therapeutic	Chloral Hydrate therapeutic dose	Drug Study Subjects are admitted to the clinical research center and receive a clinical dose of Chloral Hydrate for 5 nights (25mg/kg). On day 6 they are given a clinical dose (25mg/kg)of Dichloroacetate. (Period 3)
2B: Chloral Hydrate Therapeutic	Chloral Hydrate therapeutic dose	Subjects are given 25 mg/kg of Chloral Hydrate for five nights. Pharmacokinetics are done on days 1 and 5. (Period 4)
1A: Chloral Hydrate and DCA: Env	Chloral Hydrate environmental dose	Subjects consume Chloral Hydrate 1.5ug/kg by mouth for 5 nights. On the 6th day they consume DCA 2.5ug/kg by mouth and have blood samples drawn. (Period 1)
1B: Chloral Hydrate Env dose	Chloral Hydrate environmental dose	Drug Study Subjects are admitted to the clinical research unit and receive 1.5 ug/kg (environmental dose) of Chloral Hydrate for 5 nights. Pharmacokinetics are done on days 1 and day 5. (Period 2)

Primary Outcome Measures

Name	Time	Method
Plasma DCA (Microgram/ml) After 5 Days of Therapeutic Level Chloral Hydrate on Arm 2A.	6 Days	After 5 days of of therapeutic level Chloral Hydrate, the levels of Dichloroacetate in the plasma were measured.
Difference in Half Lives 5 Day Less One Day Exposure in Trichloroacetate	5 days	Elimination Half-life Difference on Arm 2B for 13C-Labeled trichloroacetate between day 5 (prolonged exposure) and day 1 (de novo exposure) after therapeutic level exposure to Chloral Hydrate. This outcome only applies to Period 4. Trichloroacetate is a marker, not an intervention.
Urinary Maleylacetone Levels After 5 Day Exposure to Therapeutic Chloral Hydrate (Arm 2B)	5 days	The levels were clinically indetectable at baseline and the question was whether or not substantive levels would be noted at after 5 days exposure to Chloral Hydrate. Detectable, but low levels were detected.

Secondary Outcome Measures

Name	Time	Method
Detectable DCA After Day 1 in Serum (0=No 1=Yes)	1 day	All four arms receive Chloral Hydrate on Day 1 (arms 1A and 1B environmental levels) and (arms 2A and 2B therapeutic levels). The question is could Dichloroacetate be detected in serum at the end of day 1. This analysis is purely descriptive, and no comparisons were planned.