Proceedings Article | 24 April 1996
KEYWORDS: Tissues, Molecules, Absorption, Infrared radiation, Mirrors, Infrared spectroscopy, Data modeling, Absorbance, Semiconductor lasers, Doppler effect
The goal of our work is two fold: (1) to develop a portable rapid laser based breath analyzer for monitoring metabolic processes, and (2) predict these metabolic processes through physiologically based pharmacokinetic (PBPK) modeling. Small infrared active molecules such as ammonia, carbon monoxide, carbon dioxide, methane and ethane are present in exhaled breath and can be readily detected by laser absorption spectroscopy. In addition, many of the stable isotopomers of these molecules can be accurately detected, making it possible to follow specific metabolic processes. Potential areas of applications for this technology include the diagnosis of certain pathologies (e.g. Helicobacter Pylori infection), detection of trauma due to either physical or chemical causes and monitoring nutrient uptake (i.e., malnutrition). In order to understand the origin and elucidate the metabolic processes associated with these small molecules, we are employing physiologically based pharmacokinetic (PBPK) models. A PBPK model is founded on known physiological processes (i.e., blood flow rates, tissue volumes, breathing rate, etc.), chemical-specific processes (i.e., tissue solubility coefficients, molecular weight, chemical density, etc.), and on metabolic processes (tissue site and rate of metabolic biotransformation). Since many of these processes are well understood, a PBPK model can be developed and validated against the more readily available experimental animal data, and then by extrapolating the parameters to apply to man, the model can predict chemical behavior in humans.