Modeling, identification and parameter estimation of bilirubin kinetics in normal, hemolytic and Gilbert's states

Human metabolism of bilirubin is investigated by plasma disappearance curves of 3H-bilirubin in normal, hemolytic, and Gilbert's states. A two-compartment model of bilirubin kinetics is presented. Structural identifiability of the model is investigated. Model's parameter estimation from experimental data is performed in the least-squares sense with a procedure particularly suitable for this criterion function. Some problems related to the estimation of parameters of compartmental models are discussed. Several parameters of clinical interest are derived from the model. The system has been simulated on a digital computer using the CSMP simulation language, provided with the estimation algorithm. Results obtained on a sample of two clinical situations (Gilbert's syndrome, hemolytic syndromes) and on a control group are presented. Clinical inferences drawn from the parameters obtained by the model are discussed: (i) in Gilbert's syndrome the metabolic defect possibly concerns the intrahepatic binding of bilirubin; (ii) if alterations in radiobilirubin kinetics occur under hyperhemolitic conditions, they possibly indicate that the excretory capacity of the liver has been exceeded.