Volp R F, Lage G L
Drug Metab Dispos. 1978 Jul-Aug;6(4):418-24.
In the rat, the major water-soluble biliary metabolite of digotoxin is digitoxigenin monodigitoxoside glucuronide (mono-gluc). Despite its preponderance in the bile, only small amounts of mono-gluc are found in the feces. The compound may be absorbed from the intestine as the glucuronide conjugate, or it may be hydrolyzed to the parent compound, digitoxigenin monodigitoxoside (mono); the parent compound might then be absorbed from the intestine. The purposes of this study were to determine the ability of closed duodenal and cecal strips in vivo to absorb the conjugate and the parent compound, to hydrolyze the glucuronide, and to conjugate the parent mono. Absorption of mono was found to be more rapid than mono-gluc in both intestinal locations. Absorption of mono in the cecal strip was slower than in the duodenal strip. Considerable hydrolysis of mono-gluc occurred in the cecal strip; in the duodenal strip, the net process was conjugated of the parent mono. Thus, the disappearance of mono-gluc between its appearance in the bile and excretion in the feces is explained mainly by hydrolysis in the lower intestinal tract. Paradoxically, absorption of the hydrolysis product, mono, proceeds more slowly in the lower intestine, where it is hydrolyzed, than in the duodenum, where hydrolysis does not occur.
在大鼠体内,洋地黄毒苷的主要水溶性胆汁代谢产物是洋地黄毒苷元单洋地黄毒糖苷葡萄糖醛酸苷(单葡萄糖醛酸苷)。尽管它在胆汁中占优势,但在粪便中仅发现少量的单葡萄糖醛酸苷。该化合物可能以葡萄糖醛酸苷共轭物的形式从肠道吸收,或者它可能被水解为母体化合物洋地黄毒苷元单洋地黄毒糖苷(单糖苷);然后母体化合物可能从肠道吸收。本研究的目的是确定体内封闭的十二指肠和盲肠条吸收共轭物和母体化合物、水解葡萄糖醛酸苷以及共轭母体单糖苷的能力。发现在两个肠道部位,单糖苷的吸收都比单葡萄糖醛酸苷快。盲肠条中,单糖苷的吸收比十二指肠条中慢。在盲肠条中,单葡萄糖醛酸苷发生了大量水解;在十二指肠条中,净过程是母体单糖苷的共轭反应。因此,单葡萄糖醛酸苷在胆汁中出现到粪便中排泄之间的消失主要是由下肠道中的水解作用所解释。矛盾的是,水解产物单糖苷在发生水解的下肠道中的吸收比在不发生水解的十二指肠中更慢。