Lundin S, Pierzynovski S G, Weström B R, Bengtsson H I
Department of Clinical Pharmacology, University of Lund, Sweden.
Pharmacol Toxicol. 1991 Mar;68(3):177-80. doi: 10.1111/j.1600-0773.1991.tb01218.x.
The biliary excretion of the vasopressin analogue 1-deamino-8-D-arginine vasopressin (dDAVP) was determined in the pig after three administration routes, intrajugular venous, intraportal venous and intraduodenal. In all cases the biliary excretion was less than 1% of the administered dose. The plasma/bile concentration ratio was less than 1:1. A significant first-pass effect was found when the liver was exposed to a high intraportal dose of dDAVP. Possible uptake and degradation/biotransformation was evaluated by incubating [3H]dDAVP with liver tissue slices showing that [3H]dDAVP was rapidly removed from the incubation medium. The following conclusions can be drawn from these experiments: 1) The intestinal mucosa constitutes the major barrier to intestinal absorption of dDAVP. 2) dDAVP is excreted in bile in small amounts. 3) Indirect evidence suggests that the dDAVP molecule is degraded/biotransformed in the liver at its C-terminus.
在猪身上，通过颈内静脉、门静脉和十二指肠内三种给药途径，测定了加压素类似物1-去氨基-8-D-精氨酸加压素（dDAVP）的胆汁排泄情况。在所有情况下，胆汁排泄量均小于给药剂量的1%。血浆/胆汁浓度比小于1:1。当肝脏暴露于高门静脉剂量的dDAVP时，发现有显著的首过效应。通过将[3H]dDAVP与肝组织切片孵育来评估可能的摄取和降解/生物转化，结果表明[3H]dDAVP迅速从孵育培养基中去除。从这些实验中可以得出以下结论：1）肠黏膜是dDAVP肠道吸收的主要屏障。2）dDAVP少量经胆汁排泄。3）间接证据表明，dDAVP分子在肝脏中其C端发生降解/生物转化。
