A B S T R A C T This report describes studies of bilirubin kinetics in 13 healthy young adults. The plasma content of unconjugated bilirubin-14C was determined at frequent intervals for 24-30 hr after the intravenous injection of a tracer dose of unconjugated isotopic bilirubin. Fecal and urinary radioactivity were measured for 7 days. During this time cumulative recovery averaged 96% of the injected dose. The plasma curves were processed by digital computer. For the 30 hr experimental period, a sum of three exponentials, with average half-times of 18, 81, and 578 min, was required to describe the data. Using the plasma curve integral method, the hepatic bilirubin clearance (47 +10 ml/min, mean +SD), the bilirubin production rate (3.8 ±0.6 mg/kg per day), and the mean red blood cell life span (101 ±13 days) were calculated directly from the parameters of this function. To gain further insight into the metabolism of unconjugated bilirubin, the data were also used to determine the parameters of a multicompartmental model. In the model proposed, plasma unconjugated bilirubin exchanges with two additional pools, one of which is thought to represent extrahepatic extravascular, and the other intrahepatic unconjugated bilirubin. Bilirubin is eliminated from the system via the proposed intrahepatic pool. From the data and the model, pool sizes and exchange rates between compartments were calculated, and the liver: plasma concentration gradient estimated. These studies provide a detailed analysis of the kinetics of unconjugated bilirubin in a healthy normal population and are intended to serve as a reference point for studies of abnormal states.

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On the basis of results obtained with in vitro systems, 6-aminolaevulic acid (ALA) has been found by several groups ofworkers to be a biological precursor of porphyrins and haem. The following reactions are believed to occur (Shemin & Russell,

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