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dc.contributor.authorShiels, Ryan G
dc.contributor.authorHewage, Wenu
dc.contributor.authorVidimce, Josif
dc.contributor.authorPearson, Andrew G
dc.contributor.authorGrant, Gary
dc.contributor.authorWagner, Karl-Heinz
dc.contributor.authorBulmer, Andrew C
dc.date.accessioned2021-01-04T05:59:13Z
dc.date.available2021-01-04T05:59:13Z
dc.date.issued2020
dc.identifier.issn0928-0987
dc.identifier.doi10.1016/j.ejps.2020.105684
dc.identifier.urihttp://hdl.handle.net/10072/400618
dc.description.abstractBACKGROUND AND PURPOSE: 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. EXPERIMENTAL APPROACH: 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. KEY RESULTS: 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<0.05), however, the bioavailability of BV was higher than BRS following i.p. administration (i.p. BV 28.4%, BRS 15.5%) but lower following i.d. administration (i.d. BV 0.04%, BRS 0.07%), over 180 minutes. When BRS was administered i.v., BRS had a significantly (p<0.05) longer distribution (191.9 vs 54.1 minutes) half-life compared to BV, and significantly reduced (p<0.05) volume of distribution (0.026 vs 0.145 L kg-1). As a consequence, intraperitoneal and intraduodenal administration resulted in significantly greater blood concentrations of BRS (p<0.05) over 180 minutes. Therefore, BRS may be more likely to induce antioxidant or molecular effects, when compared to BV, due to greater concentrations and a longer half-life. CONCLUSIONS AND IMPLICATIONS: Cumulatively, these data demonstrate that BRS has a superior pharmacokinetic profile when compared to BV, which is a result of its resistance to hepatic metabolism and excretion. These data therefore provide a basis to explore the capacity of BRS to protect from inflammatory pathology.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherElsevier
dc.relation.ispartofpagefrom105684
dc.relation.ispartofjournalEuropean Journal of Pharmaceutical Sciences
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences
dc.subject.fieldofresearchcode3214
dc.titlePharmacokinetics of bilirubin-10-sulfonate and biliverdin in the rat
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationShiels, RG; Hewage, W; Vidimce, J; Pearson, AG; Grant, G; Wagner, K-H; Bulmer, AC, Pharmacokinetics of bilirubin-10-sulfonate and biliverdin in the rat, European Journal of Pharmaceutical Sciences, 2020, pp. 105684
dcterms.dateAccepted2020-12-16
dc.date.updated2021-01-04T00:48:55Z
gro.description.notepublicThis publication has been entered as an advanced online version in Griffith Research Online.
gro.hasfulltextNo Full Text
gro.griffith.authorGrant, Gary D.
gro.griffith.authorBulmer, Andrew C.
gro.griffith.authorPearson, Andrew G.


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