AJP - Regulatory, Integrative and Comparative Physiology, Vol 251, Issue 6 1212-R1220, Copyright © 1986 by American Physiological Society
Kinetics of protein binding determine rates of uptake of drugs by brain
P. J. Robinson and S. I. Rapoport
A mathematical model describing the kinetics of binding and release of
substances by plasma proteins is presented. The effects of protein binding
on the uptake of substances such as drugs from the capillary network of the
brain are discussed. The model assumes equilibration between bound and free
forms of drug in arterial blood and incorporates the on-off rate constants
for the drug-protein complex and rate constants for passage of free drug
across the blood-brain barrier and for drug metabolism in the brain.
Regional cerebral blood flow and the related capillary transit time are
important parameters in the model. Analytical expressions for bound and
free drug concentrations and for the net extraction of drug are derived
where practicable, and numerical solutions also are presented. Effects of
changes in the total drug and protein concentrations in the plasma are
discussed with special reference to the uptake of bilirubin by the brain.
