Development and Use of a Mathematical Two-Pool Model of Distribution and Metabolism of 3,3′,5-Triiodothyronine in a Recirculating Rat Liver Perfusion System: Albumin Does not Play a Role in Cellular Transport*

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Abstract
To describe the T3 kinetics in a recirculating rat liver perfusion system, we have developed a mathematical two-pool model consisting of medium and liver. It appeared that all parameters of the model could be fully resolved by using the time-dependent disappearance of radioactive T3 (2 nM) from the medium only. the model calculates the T3 medium pool, the T3 liver pool, and the amount of hormone metabolized at different times after the start of the perfusion. To check the validity of the model, metabolism was also estimated from the appareance of labeled metabolites (glucuronides, sulfates, and I-) in the medium and the cumulative excretion of T3 and metabolites into the bile. The medium pool was also estimated by the product of medium volume and remaining T3 concentration, and the liver pool as the amount of T3 at time zero minus medium pool minus T3 metabolized. These results were in excellent agreement with the predicted values from the model. Taking the metabolites appearing in medium and bile together, about 38% of the total amount of T3 metabolized during 60 min was converted into T3 glucuronide, 12% into T3 sulfate, and 48% into I-, respectively, while about 3% was excreted in the bile unaltered. The results show that not all T3 transported to the liver is being metabolized, but part is bound outside the cellular compartment. This latter pool of T3 is dependent on the albumin concentration in the medium. The amount of T3 metabolized is solely determined by the free T3 concentration and is independent of total T3 or albumin concentration in the medium.