MODELING OF RESPIRATORY EXCHANGE OF POLAR-SOLVENTS

Physiologically based pharmacokinetic (pbpk) models are frequently used to describe the kinetics of inhaled gases and vapours. In these models the conducting airways of the respiratory tract are generally assumed to act as inert tubes. The function of the inert tubes is merely to conduct the vapour to the alveolar regions where the actual exchange between ambient air and body takes place. Such an 'inert tube' model may be adequate to describe the inhalation and exhalation kinetics of inert vapours, for example non-polar solvents which have a low water solubility. Experimental data suggest, however, that the 'inert tube' model may be erroneous for polar solvents which have a high water solubility. To explore this possibility further a tentative pbpk model was developed. Model structure and parameters were obtained from the literature on lung anatomy and physiology and by visual fitting to experimental acetone, carbon dioxide, diethyl ether and ethanol data. The model was written and solved by spreadsheet programming on a personal computer. Simulations were carried out to illustrate the difference between end-exhaled and alveolar air and how water solubility and workload influence the uptake and excretion kinetics of polar solvents. It is concluded that the model is valuable for predicting the lung kinetics of polar vapours under various circumstances. It may therefore be useful in the development of biological monitoring methods based on breath sampling and help us to understand and to explain experimental data.