A compartmental model for bilirubin kinetics in isolated perfused rat liver

Bilirubin kinetics were studied in an isolated, perfused rat liver system using unconjugated [14C]bilirubin (UC[14C]B) and Δ-amino[4-14C]levulinic acid (A[14C]LA) to derive a suitable compartmental model. Plasma disappearance of UC[14C]B, plasma appearance of conjugated [14C]bilirubin (C[14C]B) and biliary excretion of C[14C]B were followed for 90–120 min following injection of UC[14C]B. Hepatic content of labeled bilirubin 12 min after the injection of UC[14C]B was determined directly in five separate perfusion experiments. UCB was found to reflux back to plasma from liver in two experiments using A[14C]LA. Bilirubin binding to red blood cells (6–8% of the perfusate level) and the components of the perfusion apparatus (4–6% of perfusate level) was estimated by performing a control experiment without the liver. A six compartment model was necessary and adequate to explain the experimental data and current knowledge of bilirubin metabolism: (1) UCB bound to red blood cells and the perfusion apparatus, (2) plasma UCB, (3) liver UCB, (4) liver CB, (5) plasma CB, and (6) bile CB. The proposed model could serve as a reference point for studies of bilirubin kinetics in whole animals for normal and abnormal states.