Pharmacokinetics of bilirubin-10-sulfonate and biliverdin in the rat

• Published in: European journal of pharmaceutical sciences 2021-04, Vol.159, p.105684, Article 105684
• Main Authors: Shiels, Ryan G., Hewage, Wenu, Vidimce, Josif, Pearson, Andrew G., Grant, Gary, Wagner, Karl-Heinz, Bulmer, Andrew C.
• Format: Article
• Language: English
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2020.105684

Biliverdin (BV) administration induces antioxidant and anti-inflammatory effects, with previous reports also identifying anti-anaphylactic potential. Interestingly however, intra-duodenal administration of BV in rats leads to the formation of bilirubin-10-sulfonate (BRS), which might be responsible for BV's purported effects. This study aimed to assess the intravenous, intraperitoneal and intraduodenal pharmacokinetics of BRS and BV in order to assess their therapeutic potential in future studies. Bile and venous blood were intermittently collected before and after administration, which was subsequently analysed using liquid chromatography-mass spectrometry for quantification of bile pigment concentrations. Interestingly, i.p. BRS administration led to a greater circulating concentration and had a reduced excretion rate, which resulted in a substantially elevated AUC180 when compared to BV administration. Furthermore, BRS was excreted intact in the bile, in contrast to BV which was excreted after chemical reduction and conjugation. Intraperitoneal and intraduodenal administration substantially increased blood BRS concentrations (p