Estimation of tissue-to-plasma partition coefficients used in physiological pharmacokinetic models.

An important parameter in the development of pharmacokinetic models is the ratio of tissue drug concentration to the concentration of the drug in the arterial plasma or the effluent plasma. The relationship between these two tissue/plasma ratios is derived analytically for different routes of drug administration. The two are equal only in compartments with no elimination when the drug is infused at constant rate. For other routes of administration, the two ratios are identical in all compartments only when there is no elimination process. The tissue/plasma concentration ratios for infusion equilibrium are not equal to the corresponding values for the postdistribution phase after an intravenous bolus injection. When the plasma concentration for infusion and injection are the same, more drug will appear in the lung during infusion steady state than during the postdistribution equilibrium. The reverse is true for the other organs. The importance of properly defining the tissue/plasma ratio and its implication for pharmacokinetic modeling are discussed. The results may have important therapeutic implications for the availability of drugs using different routes of administration.