Bile pigment pharmacokinetics and absorption in the rat: therapeutic potential for enteral administration
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Background 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.
British Journal of Pharmacology
Animal Physiology - Systems