Blood flow tissue distribution kinetics

The previously described equations are characteristic of blood flow rate-limited models it is assumed that xenobiotics cross the cell membrane by simple diffusion and that equilibrium takes place instantaneously between blood and tissue compartments. This assumption is valid for a great number of chemicals. For certain xenobiotics, however, the kinetics of tissue uptake are not consistent with blood flow rate-limited processes since their distribution in a given tissue is limited by the resistance of the cell membrane to the passage of a xenobiotic. In these cases, the basic equation should account for such phenomena to describe adequately the time course of the xenobiotic disposition in the tissue. 

The distribution into different tissues is a kinetic process governed by the organ blood flows, binding to tissues and plasma proteins, regional pH gradients, and permeability of cell membranes. The extent of distribution depends on how extensively a compound can go into tissues and how tightly it is bound to by tissues, as shown by the following equation ... 

Pharmacokinetic models describe the biological processes of absorption, distribution, metabolism, and excretion of exogenous compounds. With the exception of absorption into and across the skin, absorption, distribution, metabolism, and elimination are essential processes that also occur with nutrients and endogenous compounds. Many of these processes can become nonlinear with increasingly higher exposure concentrations. Pulmonary absorption can be limited by respiratory rates. Metabolism can often show Michaelis-Menten or saturable kinetics. Distribution can be limited by the affinity of the chemical for a specific tissue or by blood flow. 

---