On model and data requirements for determining the bioavailability of oral therapeutic agents: application to gut absorption of thyroid hormones.

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.