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

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.