The Effects of Atazanavir-induced Hyperbilirubinemia During Human Endotoxemia
Status:
Completed
Trial end date:
2015-07-01
Target enrollment:
Participant gender:
Summary
Excessive inflammation, production of free radicals and vascular injury are considered the
main contributors to the development of organ dysfunction in patients with severe infections
and sepsis. The endogenously produced unconjugated bilirubin is one of the most powerful
anti-oxidants of the human body and the administration of bilirubin in animal experiments has
been shown to protect from inflammation-induced death. However, bilirubin for human
administration is not yet available. Therefore, we wish to exploit one of the side effects of
atazanavir, a registered drug currently used as a protease inhibitor in HIV infected
patients. Atazanavir inhibits the enzyme UPD glucuronosyl transferase enzyme (UGT1A1) and
therefore increases endogenously produced bilirubin levels moderately. To study the effect of
hyperbilirubinemia during inflammation we will apply the human endotoxemia model. The human
endotoxemia model permits elucidation of key players in the immune response to a gram
negative stimulus in vivo, therefore serving as a useful tool to investigate potential novel
therapeutic strategies in a standardized setting. We hypothesize that atazanavir-induced
hyperbilirubinemia has beneficial anti-inflammatory and vascular effects during human
endotoxemia.