1. The validity of a two-compartment pharmacokinetic model for the estimation of the hepatic extraction ratio of Indocyanine Green was tested in six patients with cirrhosis of the liver.
2. No agreement was found between the value of the hepatic extraction ratio measured directly and that calculated using the two-compartment model.
3. To investigate the reasons for the failure of the model, an extended sampling period was used to define the time course of Indocyanine Green in plasma in six healthy subjects and in six patients with cirrhosis of the liver after a bolus injection of the dye.
4. Indocyanine Green was measurable in the plasma for up to 10 h after injection in healthy subjects, and up to 48 h after injection in the patients. The plasma elimination curve in both groups was best described by a triexponential function.
5. The clearance of Indocyanine Green calculated using data collected in the first 20 min after injection overestimated that calculated using data collected for as long as Indocyanine Green was measurable in the plasma. In the patients with cirrhosis the mean overestimate was 87%.
6. Thus, a two-compartment pharmacokinetic model was inappropriate for the description of the disposition of Indocyanine Green and estimates of the hepatic extraction ratio obtained using this model in patients with cirrhosis were inaccurate.