Quantitative studies of the delivery of hepatic-synthesized bilirubin to plasma utilizing δ-aminolevulinic acid-4-14C and bilirubin-3H in man

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Abstract
After the simultaneous intravenous administration of unconjugated bilirubin-3H and δ-aminolevulinic acid-4-14C, the plasma disappearance curves of unconjugated bilirubin-3H and the plasma appearance curves of biosynthesized unconjugated bilirubin-14C have been defined in seven patients, three of whom had acute intermittent porphyria (AIP). The incorporation of 14C into plasma unconjugated bilirubin, derived by an analysis which involves deconvolution of the two plasma curves, varied between 13.1 and 23.5% (mean 19.3%) of the injected dose in the nonporphyric patients and between 5.4 and 13.6% (mean 8.3%) of the injected dose in the porphyric patients. In five of the patients, the stercobilin-14C specific activity in a pooled specimen of feces was measured, enabling the following further values to be calculated: (a) the total 14C radioactivity incorporated into bilirubin (21.0 and 25.3% [mean 23.2%] of the injected dose in two of the nonporphyric patients and between 8.5 and 25.3% [mean 14.2%] of the injected dose in the porphyric patients), and (b) the proportion of hepatic synthesized bilirubin delivered directly to plasma in the unconjugated form (between 0.520 and 0.904; mean for nonporphyric patients 0.712; mean for porphyric patients 0.614). The results demonstrate that a large proportion of bilirubin derived from hepatic hemes passes through the plasma in the unconjugated form before conjugation and secretion into bile.