Article date: February 2018
By: Douwe Dekker, Mirrin J. Dorresteijn, Marieke E. B. Welzen, Simone Timman, Peter Pickkers, David M. Burger, Paul Smits, Frank A. D. T. G. Wagener, Frans G. M. Russel in Volume 84, Issue 2, pages 268-279
Aims
Preclinical results suggest therapeutic potential of mild hyperbilirubinemia in T2DM and cardiovascular disease. Translational data are limited, because an appropriate bilirubin formulation for parenteral human use is lacking. Considering its use in both clinical practice and medical research in the past, we explored the feasibility to reintroduce parenteral bilirubin for translational experiments.
Methods
We developed a preparation method in accordance with good manufacturing practice and evaluated the parenteral applicability in healthy volunteers (n = 8). Explorative pharmacokinetic and safety data were compared to the results from a literature study on the former parenteral use of bilirubin. Bilirubin was administered intra‐arterially to raise the local plasma concentration in the forearm vascular bed (n = 4) and intravenously to raise the systemic plasma concentration (n = 4). Finally, pharmacokinetic characteristics were studied following a single bolus infusion (n = 3).
Results
During parenteral application, no side effects occurred. Adverse events mentioned during the two‐week observation period were in general mild and self‐limiting. Three more significant adverse events (appendicitis, asymptomatic cardiac arrhythmia and atopic eczema) were judged unrelated by independent physicians.
Conclusions
Supported by previous reports, our data suggest that it is both feasible and safe to perform translational experiments with parenteral albumin bound bilirubin.
DOI: 10.1111/bcp.13458
View this article