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1. The disposition of an intravenous bolus of indocyanine green (ICG) has been studied in healthy man and baboons using a novel analysis of a two compartment pharmacokinetic model. 2. This analysis enabled the hepatic extraction ratio (ER) of dye to be determined solely from the plasma disappearance curve, and the ER determined did not differ from that measured by hepatic vein catheterization. 3. When compared with clearance measured at steady state, the two compartment model gave a significantly more accurate determination of plasma clearance than did the conventional one compartment model. 4. It is concluded that, in health, liver blood flow may be calculated accurately and non-invasively after a single intravenous injection of ICG.

1. The fasting plasma disappearance curve of [14C]glycocholic acid after intravenous injection was compared in nine normal subjects with that obtained 100 min after a standard liquid test meal. 2. Plasma disappearance curves of indocyanine green were determined in 13 normal subjects under the same conditions. 3. Plasma clearances were significantly increased after the meal for both [14C]glycocholic acid (median 455 ml min--1 m--2, range 376--672 increased to 704, 528--1968; P less than 0.01) and indocyanine green (359, 227--473 increased to 435, 358--985; P less than 0.01). 4. Median initial volume of distribution was unaltered, but in four subjects it was greatly increased after the meal, although no alteration in plasma volume, measured with Evans blue dye, was observed. 5. The increased postprandial plasma clearance of glycocholic acid is probably due to an increase in liver blood flow, and suggests that in health this part of the enterohepatic circulation of bile acids also varies with meals.

The clearance, half-life time, fractional elimination rate and distribution volume of indocyanine green (10 mg . m-2) were measured in 20 control subjects and 63 patients with histologically confirmed liver disease. Mean clearance was significantly impaired only in the patients with alcoholic and primary biliary cirrhosis; in those with active chronic hepatitis, with or without cirrhosis, or with acute hepatitis, clearance was normal. However, half-life time and fractional elimination rate were impaired in all but one group of patients. This discrepancy arose because of a significantly increased distribution volume in all groups with chronic liver diseases except primary biliary cirrhosis. Thus, in chronic liver disease, half-life times and fractional elimination rates do not necessarily reflect hepatic uptake; measurement of clearance is therefore to be preferred.