Bile pigment pharmacokinetics and absorption in the rat: therapeutic potential for enteral administration

摘要: BACKGROUND AND PURPOSE Bilirubin and biliverdin possess antioxidant anti-inflammatory properties their exogenous administration protects against the effects of inflammation trauma in experimental models. Despite therapeutic potential bile pigments, little is known about vivo parenteral or enteral absorption after administration. This study investigated pharmacokinetics pigments i.v., i.p. intraduodenal (i.d.) addition to metabolism routes excretion. EXPERIMENTAL APPROACH Anaesthetized Wistar rats had duct, jugular portal veins cannulated. Bile were infused circulating concentrations/biliary excretion measured over 180 min. KEY RESULTS After i.v. unconjugated bilirubin, bilirubin ditaurate, plasma concentrations decreased exponentially time. Subsequently, native metabolized compounds appeared bile. When administered i.p., absolute bioavailabilities equalled 14.0, 16.1 33.1%, respectively, correspondingly 38, 28 34% same pigment doses excreted Administration ditaurate i.d. increased systemic bioavailability 1.0 2.0%, respectively. Correspondingly, 2.7 4.6%, Biliverdin was rapidly these products absorbed via urine bile. CONCLUSIONS IMPLICATIONS from peritoneal duodenal cavities demonstrate new for treatment inflammatory traumatic pathology. Oral may lead production active metabolite that protect inflammation/complement activation.