Evaluation of various models of hyaluronan kinetics for assessment of liver function

Abstract

The purpose of this study of various models of hyaluronan kinetics has been to find the most appropriate model for estimation of parameters which characterize liver endothelial cell function.

Five theoretical models for serum hyaluronan distribution and elimination were evaluated by computer analysis of serial measurements of the mass concentration of hyaluronan in serum following an intravenous bolus dose.

Three of the models were based on one-compartment distribution of intravenously injected hyaluronan. Model 1A, with assumed first-order elimination, was found to be compatible with measured data and had identifiable parameters. Model 1B, with assumed non-linear Michaelis-Menten kinetics, was also found to be compatible but the Michaelis-Menten constant (K_m) was not well determined. In model 1C, with non-linear Michaelis-Menten elimination kinetics, K_m was set to a fixed value of 340 µ;g1⁻¹, and the remaining parameters were well determined and the model was found to be compatible.

Two models with an assumed two-compartment distribution of intravenously injected hyaluronan, were not acceptable due to unidentified parameters not discriminating between patients and healthy persons.

In conclusion, model 1C, with one-compartment distribution and non-linear Michaelis-Menten kinetics, best fulfilled the criteria of validity and was accepted for further evaluation of clinical materials.

Key Words:

• elimination parameters
• healthy
• hyaluronan
• hyaluronate
• hyaluronic acid
• kinetics
• liver disease
• loading test