Incorporation of first-order uptake rate constants from simple mammillary models into blood-flow limited physiological pharmacokinetic models via extraction efficiencies.

Incorporation of First-Order Uptake Rate Constants from Simple Mammillary Models into Blood-Flow Limited Physiological Pharmacokinetic Models via Extraction Efficiencies. W. L. Roth, L. W. D. Weber, and K. Rozman (1995). Pharm. Res. 263-269. First-order rate constants obtained from classical pharmacokinetic models correspond to mammillary systems in which all of the blood (or plasma) 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 central compartment multiplied by a rate constant, which is not limited in magnitude by the blood flow, or the rate at which chemicals from the blood are delivered to the peripheral compartment. Most of the physiologically-based models published to date dispense with some of the information available from mammillary models by assuming that all of the chemical delivered by the flow of blood rapidly equilibrates and can be taken up by the tissue under the control of a "partition coefficient" (Rij = Cj/Ci). We show that the partition coefficient alone does not retain the uptake rate (kji) information available from a classical mammillary model, but that the uptake rate information can be incorporated via unitless extraction efficiency parameters, epsilon j.