Half-Life of Bilirubin
The half-life of unconjugated bilirubin in normal adults is extremely short at approximately 18 minutes (with additional slower phases at 81 and 578 minutes), while bilirubin covalently bound to albumin (delta bilirubin) has a dramatically prolonged half-life of 19-21 days, matching albumin's turnover rate. 1, 2
Unconjugated Bilirubin Kinetics in Normal Adults
In healthy adults, plasma unconjugated bilirubin follows a three-phase elimination pattern with half-times of 18 minutes (initial rapid phase), 81 minutes (intermediate phase), and 578 minutes (terminal phase). 1
The rapid initial clearance reflects hepatic uptake and conjugation, with hepatic bilirubin clearance averaging 47 ±10 ml/min in normal individuals. 1
This multi-exponential clearance pattern represents bilirubin exchange between plasma, extrahepatic extravascular pools, and intrahepatic compartments before final elimination. 1
Delta Bilirubin (Albumin-Bound Bilirubin)
When bilirubin becomes covalently attached to albumin during hepatobiliary disease or biliary obstruction, it circulates with a half-life of 19-21 days, identical to albumin's metabolic half-life. 2, 3
This prolonged half-life explains why hyperbilirubinemia can persist for weeks after resolution of the underlying hepatobiliary disease—the delta bilirubin fraction cannot be rapidly cleared. 2, 3
Delta bilirubin is included in the "direct bilirubin" measurement, which is why direct hyperbilirubinemia may not correlate with current disease activity in recovering patients. 3
Special Populations and Photoproducts
Neonatal Phototherapy Context
During phototherapy, bilirubin is converted to lumirubin, which has a much shorter half-life of 80-158 minutes, allowing for rapid elimination through bile. 4
This rapid clearance of lumirubin makes it the most important photoproduct for bilirubin elimination during phototherapy treatment. 4
In Vitro Photodegradation
- Under controlled laboratory conditions at 37°C, bilirubin photodegradation half-life ranges from 17-63 minutes depending on wavelength (500 nm vs 390 nm respectively). 5
Clinical Implications
The dramatic difference between unconjugated bilirubin's 18-minute half-life and delta bilirubin's 19-21 day half-life is critical for interpreting persistent hyperbilirubinemia after acute liver injury resolution. 1, 2
In patients recovering from cholestatic liver disease, elevated direct bilirubin may reflect delta bilirubin accumulation rather than ongoing hepatobiliary dysfunction. 3, 2
The short half-life of unconjugated bilirubin means that elevated levels indicate either increased production (hemolysis) or impaired hepatic uptake/conjugation occurring in real-time. 1