AJP - Gastrointestinal and Liver Physiology, Vol 244, Issue 6 583-G589, Copyright © 1983 by American Physiological Society
Saturation kinetics in hepatic drug removal: a statistical approach to functional heterogeneity
L. Bass
Extraction of drugs and other substrates from blood passing through the
intact liver (or other capillary beds), inferred from samples taken at the
organ inlet and outlet, is influenced by two kinds of heterogeneity of
capillaries: transverse and longitudinal with respect to the direction of
blood flow. The transverse heterogeneity is exemplified by arteriovenous
shunts of the extracting system; the longitudinal one by zones of liver
function. These two clinically interesting examples are among transverse
and longitudinal distributions of capillary properties that can be inferred
from the way the organ transforms the influx of a substance (or of a pair
of substances interacting via liver cells) into the outflux over a range of
input concentrations or of rates of blood flow. Mathematical and
statistical ideas recently developed to implement this program in terms of
saturation kinetics of uptake are reviewed and elucidated in relation to
key experiments, data analysis, and statistical hypothesis testing.
