title: Bile pigment pharmacokinetics and absorption in the rat: therapeutic potential for enteral administration.
abstract: OBJECTIVE
  Bilirubin and biliverdin possess antioxidant and anti-inflammatory properties and their exogenous administration protects against the effects of inflammation and trauma in experimental models. Despite the 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 pigments after i.v., i.p. and intraduodenal (i.d.) administration in addition to their metabolism and routes of excretion.
  
  
  METHODS
  Anaesthetized 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 min. KEY RESULTS After i.v. administration of unconjugated bilirubin, biliverdin and bilirubin ditaurate, their plasma concentrations decreased exponentially over time. Subsequently, native and metabolized compounds appeared in the bile. When administered i.p., their absolute bioavailabilities equalled 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. Administration of unconjugated bilirubin and bilirubin ditaurate i.d. increased their portal and systemic concentrations and their systemic bioavailability equalled 1.0 and 2.0%, respectively. Correspondingly, 2.7 and 4.6%, of the doses were excreted in the bile. Biliverdin was rapidly metabolized and these products were absorbed and excreted via the urine and bile.
  
  
  CONCLUSIONS
  Bile pigment absorption from the peritoneal and duodenal cavities demonstrate new routes of administration for the treatment of inflammatory and traumatic pathology. Oral biliverdin administration may lead to the production of active metabolite that protect from inflammation/complement activation.
authors.affiliation: Heart Foundation Research Centre, Griffith Health Institute, Griffith University, Southport, Queensland, Australia. a.bulmer@griffith.edu.au
authors.forename: A C
authors.initials: AC
authors.lastname: Bulmer
authors.forename: J S
authors.initials: JS
authors.lastname: Coombes
authors.forename: J T
authors.initials: JT
authors.lastname: Blanchfield
authors.forename: I
authors.initials: I
authors.lastname: Toth
authors.forename: R G
authors.initials: RG
authors.lastname: Fassett
authors.forename: S M
authors.initials: SM
authors.lastname: Taylor
mesh_terms: D000042:Absorption; D000818:Animals; D001646:Bile / Q000737:chemistry; D001663:Bilirubin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D001664:Biliverdine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D004386:Duodenum / Q000378:metabolism; D005766:Gastrointestinal Contents; D007267:Injections; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D010529:Peritoneal Cavity / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013654:Taurine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D013654:Taurine; C054146:bilirubin ditaurine; D001664:Biliverdine; D001663:Bilirubin