Computer simulations of physiologically based pharmacokinetic models are being used to study the uptake and metabolism of compounds administered by inhalation. The application of these models to specific compounds requires two types of compound specific data; tissue partition coefficients and metabolic constants. Systems for making these measurements have been developed by adapting the designs used by other laboratories. Tissue partition coefficients are determined by measuring the partitioning between tissue homogenates and the headspace in sealed vials. Metabolic rate constants are measured by monitoring the removal by the test animals of the compound from the atmosphere of a sealed recirculating exposure system. A computer simulation of the test animals and the exposure system is used to estimate the metabolic rates from these measurements. Models are validated against blood concentration measurements taken at various time points during inhalation exposures.
