INCORPORATION OF FIRST-ORDER UPTAKE RATE CONSTANTS FROM SIMPLE MAMMILLARY MODELS INTO BLOOD-FLOW LIMITED PHYSIOLOGICAL PHARMACOKINETIC MODELS VIA EXTRACTION EFFICIENCIES

First-order rate constants obtained from classical pharmacokinetic mod els correspond to mammillary systems in which all of the blood (Or pla sma) is assumed to be located in a central compartment. In such models the rate at which chemicals are transported out of this pool and into another compartment is the product of the mass of chemical in the cen tral compartment multiplied by a rate constant, which is not limited i n magnitude by the blood flow, or the rate at which chemicals from the blood are delivered to the peripheral compartment. Most of the physio logically-based models published to date dispense with some of the inf ormation available from mammillary models by assuming that all of the chemical delivered by the flow of blood rapidly equilibrates and can b e taken up by the tissue under the control of a ''partition coefficien t'' (R(ij) = C-j/C-i). We show that the partition coefficient alone do es not retain the uptake rate (k(ji)) information available from a cla ssical mammillary model, but that the uptake rate information can be i ncorporated via unitless extraction efficiency parameters, epsilon(j).