AJP - Regulatory, Integrative and Comparative Physiology, Vol 236, Issue 3 137-R141, Copyright © 1979 by American Physiological Society
On model and data requirements for determining the bioavailability of oral therapeutic agents: application to gut absorption of thyroid hormones
J. J. DiStefano 3rd and P. H. Mak
A two-pool model is proposed as a first approximation of the dynamics of
thyroid hormone dissolution and absorption in the human gut. It is shown
that this model, or any more complex one of the same process, must be
imbedded in a larger whole-body model for the purpose of quantifying its
parameters. Parameter identification experiments are designed with the aid
of identifiability analysis and a complete quantification is obtained, for
both triiodothyronine (T3) and thyroxine (T4) absorption, using kinetic
data obtained from the literature. The average percent absorption of oral
dosages calculated from the model for T3 (95.8%) and for T4 (49.3%) are
exceptionally close to reported measured values. Other data not used in
model development also serve to validate the results, for use in
applications not demanding greater physiological detail, such as for
determining the bioavailability of orally administered hormones, or for the
"inverse problem," computing optimal dosage regimens for hormone therapy.
