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dc.contributor.authorBulmer, Andrewen_US
dc.contributor.authorCoombes, JSen_US
dc.contributor.authorBlanchfield, JTen_US
dc.contributor.authorToth, Ien_US
dc.contributor.authorFassett, RGen_US
dc.contributor.authorTaylor, SMen_US
dc.date.accessioned2017-04-24T13:13:50Z
dc.date.available2017-04-24T13:13:50Z
dc.date.issued2011en_US
dc.date.modified2012-03-20T22:55:09Z
dc.identifier.issn14765381en_US
dc.identifier.doi10.1111/j.1476-5381.2011.01413.xen_US
dc.identifier.urihttp://hdl.handle.net/10072/43699
dc.description.abstractBackground and purpose: Bilirubin and biliverdin possess antioxidant and anti-inflammatory properties and their exogenous administration protects against an array of inflammatory and traumatic experimental models. Despite the versatile therapeutic potential of bile pigments, little is known about their in vivo parenteral or enteral absorption after exogenous administration. This study investigated the absorption and pharmacokinetics of bile pigment administration after i.v., i.p. and i.d. administration in addition to their metabolism and routes of excretion. Experimental approach: Anaesthetised Wistar rats had their bile duct, jugular and portal veins cannulated. Bile pigments were infused and their circulating concentrations/biliary excretion were measured over 180 minutes. Key results: When unconjugated bilirubin, biliverdin and bilirubin ditaurate were administered intravenously, their plasma concentrations decreased exponentially over time. Native and metabolised compounds subsequently appeared in the bile. When administered intraperitoneally, their absolute bioavailabilities equaled 14.0, 16.1 and 33.1%, respectively and correspondingly 38, 28 and 34% of the same bile pigment doses were excreted in the bile. Intraduodenal unconjugated bilirubin and bilirubin ditaurate administration increased their portal and systemic concentrations and their systemic bioavailability equaled 1.0 and 2.0%, respectively. Correspondingly, 2.7 and 4.6% of the doses were excreted in the bile. Biliverdin was rapidly metabolised and these products were absorbed and excreted via the urine and bile. Conclusions and implications: Bile pigment absorption from the peritoneal and duodenal cavities demonstrates new routes of administration for the treatment of inflammatory and traumatic pathology. Oral biliverdin administration, leading to its metabolism/absorption, might serve as a prodrug, protecting from inflammation/complement activation.en_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_US
dc.languageEnglishen_US
dc.publisherJohn Wiley & Sons Ltden_US
dc.publisher.placeUnited Statesen_US
dc.relation.ispartofstudentpublicationNen_US
dc.relation.ispartofpagefrom1857en_US
dc.relation.ispartofpageto1870en_US
dc.relation.ispartofissue7en_US
dc.relation.ispartofjournalBritish Journal of Pharmacologyen_US
dc.relation.ispartofvolume164en_US
dc.rights.retentionYen_US
dc.subject.fieldofresearchAnimal Physiology - Systemsen_US
dc.subject.fieldofresearchBasic Pharmacologyen_US
dc.subject.fieldofresearchcode060603en_US
dc.subject.fieldofresearchcode111501en_US
dc.titleBile pigment pharmacokinetics and absorption in the rat: therapeutic potential for enteral administrationen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.facultyGriffith Health, School of Medical Scienceen_US
gro.date.issued2011
gro.hasfulltextNo Full Text


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