Development and Validation of a Physiologically Based Pharmacokinetic Model of Chloral Hydrate and Its Main Metabolites
Abstract
Chloral hydrate is a synthetic sedative/hypnotic drug used in human medicine. It is also generated as a chlorination by-product in drinking water and is produced in the organism from an environmental pollutant - trichloroethylene. Chloral, along with trichioroethylene, are occurring as environmental contaminants at the Air Force, Navy, and Army installations. This report describes the development of an interlinked physiologically based pharmacokinetic model of chloral and its main metabolites, mathematical description of the interlinking between sub-models for each metabolite, model verification with data from the literature and its experimental calibration in B6C3Fl mice. The developed model described successfully the pharmacokinetics of chloral, trichloroethanol and its glucuronide in mice and dogs. It seems that one adequately validated in humans, the developed model might be applied for a computer-aided simulation of body levels of chloral hydrate in a therapeutic situation and for the estimate of toxicokinetics of its active metabolites generated during the environmental pollution scenario.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 1995
- Accession Number
- ADA360728
Entities
People
- Brendan L. Garrity
- Connie S. Seckel
- Janusz Z. Byczkowski
- Jason R. Creech
- Richard K. Black