Remmel R P, Elmer G W
Res Commun Chem Pathol Pharmacol. 1981 Dec;34(3):503-14.
The excretion and metabolism of 14C-warfarin in rats was examined in a crossover experiment, the first phase consisting of treatment with normal saline, the second phase using the same animals given neomycin, bacitracin, and tetracycline orally. Urine and feces were collected every 24 hours for 72 hours and examined for warfarin and its metabolites, both unconjugated and conjugated. Significantly more radioactivity was eliminated in th feces of antibiotic-treated rats. The feces of antibiotic-treated rats contained only trace amounts of beta-glucuronidase activity. Urine contained a similar ratio of unconjugated to conjugated radioactivity in both treatment groups, but the antibiotic-treated animals had significantly larger amount of conjugates in their feces. Examination of metabolic profiles of conjugated and unconjugated fractions revealed significantly fewer hydroxylated metabolites in antibiotic-treated rats, especially in the feces. The lower amount of hydroxylative metabolism in attributed to a reduction in gut flora-medicated interohepatic recycling caused by the antibiotics.
在一项交叉实验中研究了大鼠体内14C-华法林的排泄和代谢情况，第一阶段用生理盐水处理，第二阶段对同一批动物口服新霉素、杆菌肽和四环素。每24小时收集72小时的尿液和粪便，检测华法林及其未结合和结合的代谢产物。抗生素处理组大鼠粪便中消除的放射性明显更多。抗生素处理组大鼠的粪便中仅含有微量的β-葡萄糖醛酸酶活性。两个处理组尿液中未结合放射性与结合放射性的比例相似，但抗生素处理组动物粪便中的结合物含量明显更高。对结合和未结合部分的代谢谱进行检测发现，抗生素处理组大鼠尤其是粪便中的羟基化代谢产物明显减少。羟基化代谢量较低归因于抗生素导致肠道菌群介导的肝肠循环减少。
