Furukawa H, Imventarza O, Venkataramanan R, Suzuki M, Zhu Y, Warty V S, Fung J, Todo S, Starzl T E
Department of Surgery, School of Medicine, University of Pittsburgh, PA 15213.
Transplantation. 1992 Apr;53(4):722-5. doi: 10.1097/00007890-199204000-00002.
Mongrel or beagle dogs were submitted to bile duct ligation, or to extraenteric biliary diversion by means of choledochoureterostomy. The kinetics of intravenously administered FK506 was not changed from control status two weeks after bile duct ligation, but the bioavailability of orally administered FK506 was nearly quadrupled. Following oral administration, the absorption of FK506 was highly variable. The results indicate that in dogs FK506 is absorbed from the intestine just as efficiently in the absence of enteric bile and in presence of exogenous bile salt supplement when compared with its absorption in presence of normal bile drainage. These findings with FK506 are different from those with cyclosporine after biliary obstruction or diversion and will have important practical as well as experimental ramifications.
杂种犬或比格犬接受胆管结扎术，或通过胆总管输尿管吻合术进行肠外胆汁转流术。胆管结扎术后两周，静脉注射FK506的动力学与对照状态相比没有变化，但口服FK506的生物利用度几乎增加了四倍。口服后，FK506的吸收差异很大。结果表明，与正常胆汁引流情况下相比，在犬类中，FK506在没有肠内胆汁且补充外源性胆盐的情况下，从肠道吸收的效率相同。FK506的这些发现与胆管梗阻或转流后环孢素的发现不同，将产生重要的实际和实验影响。
