Bilirubin treatment in humans; a study on safety and dose finding.

Parenteral
administration of bilirubin has been applied frequently in the past. For
now, bilirubin is not commercially available for human research. As
several observational studies suggest a beneficial effect of bilirubin
with respect to for example cardiovascular disease, we will reintroduce
bilirubin for parenteral human use to explore these findings. The
current study is performed to assess pharmacokinetic data on
intra-arterial and intravenous administration in healthy individuals.
Furthermore, side effects will be monitored.

Multiple observational and animal studies suggest a therapeutic effect of bilirubin in various diseases. To verify this suggestion, intervention studies with experimental hyperbilirubinemia are needed. The current study explores the applicability of the parenteral use of bilirubin, both with regards to safety and pharmacokinetics.

The first phase of the study includes the intra-arterial administration of bilirubin. Subjects will be examined subsequently with invariably at least one week in between. Plasma samples will be taken on a regular base to study both local and systemic rises of the bilirubin level. On the condition that no adverse effects are noted, subjects will be re-examined in a second phase in which larger doses of bilirubin will be administered intravenously. Again, subjects will be examined subsequently with invariably at least one week in between. Plasma samples will be taken on a regular base to study systemic rises of the bilirubin level.

Increasing amounts of bilirubin will be administered both intra-arterially (first phase - low total dose) and intravenously (second phase - high total dose). Dose levels will remain far below those levels reported safe in literature.