Bile pigment pharmacokinetics and absorption in the rat: therapeutic potential for enteral administration
Bile pigment pharmacokinetics and absorption in the rat: therapeutic potential for enteral administration
复制标题
DOI：
10.1111/j.1476-5381.2011.01413.x
复制
发表时间：
2011-12-01
影响因子：
7.3
通讯作者：
Taylor, S. M.
中科院分区：
文献类型：
--
作者：
Bulmer, A. C.;Coombes, J. S.;Taylor, S. M.
胆红素和胆绿素具有抗氧化和抗炎特性，它们的外源性给药在实验模型中可保护免受炎症和创伤的影响。尽管胆色素的治疗潜力，很少有人知道他们在体内肠外或肠内吸收外源性给药后。本研究研究了静脉注射后胆色素的吸收和药代动力学，i. p.和十二指肠内（i.d.）实验方法麻醉的Wistar大鼠的胆管、颈静脉和门静脉插管。输注胆色素，并在180 min内测量其循环浓度/胆汁排泄。关键词静脉注射未结合胆红素、胆绿素和胆红素二月桂酸盐后，其血浆浓度随时间呈指数下降。随后，胆汁中出现天然和代谢化合物。当腹腔注射时，它们的绝对生物利用度分别为14.0、16.1和33.1%，相应地，相同胆色素剂量的38、28和34%经胆汁排泄。非结合胆红素和二月桂酸胆红素i.d.给药增加了门静脉和全身浓度，全身生物利用度分别为1.0%和2.0%。相应地，2.7%和4.6%的剂量经胆汁排泄。胆绿素被迅速代谢，这些产品被吸收，并通过尿液和bile.CONCLUSIONS和IMPLICATIONSBile色素吸收从腹膜和十二指肠腔排泄证明新的给药途径，用于治疗炎症和创伤性病理。口服胆绿素给药可能导致产生活性代谢物，保护免受炎症/补体激活。
BACKGROUND AND PURPOSEBilirubin 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.EXPERIMENTAL APPROACHAnaesthetized 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 RESULTSAfter 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 AND IMPLICATIONSBile 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.