Pellegrin P L, Lesne M
Drug Metab Dispos. 1984 Mar-Apr;12(2):235-41.
After in vitro perfusion of rabbit isolated liver with an emulsion of perfluorocarbon containing [3H]gitoxin, the radioactivity in the liver and in the bile was the sum of that contained in a volatile fraction (tritiated water due to metabolism of gitoxin) and that contained in a nonvolatile fraction (gitoxin and its metabolites). This fraction was divided, by differential extraction, into two groups: liposoluble (dichloromethane soluble) compounds, including unchanged gitoxin and lipophilic metabolites (amounting to 50% in the liver and to 5% in the bile), and hydrosoluble (dichloromethane insoluble) metabolites (50% in the liver, 95% in the bile). Three types of metabolites were found in the hydrosoluble fraction. One type was sensitive to beta-glucuronidase and arylsulfatase hydrolysis, a second type was insensitive to enzymatic hydrolysis but sensitive to acid hydrolysis, and a third type was insensitive to both enzymatic and acid hydrolysis. The liposoluble compounds and the conjugates sensitive to enzymatic hydrolysis were analyzed by reversed phase high performance liquid chromatography and found to comprise a wide variety of metabolites. The present study demonstrates that gitoxin uptake by the liver is followed by a fast and extensive metabolism to highly polar metabolites that are rapidly excreted into the bile.
用含有[³H]地高辛的全氟碳乳液对兔离体肝脏进行体外灌注后，肝脏和胆汁中的放射性是挥发性部分（地高辛代谢产生的氚水）和非挥发性部分（地高辛及其代谢产物）所含放射性之和。通过差异萃取，该部分被分为两组：脂溶性（可溶于二氯甲烷）化合物，包括未变化的地高辛和亲脂性代谢产物（在肝脏中占50%，在胆汁中占5%），以及水溶性（不溶于二氯甲烷）代谢产物（在肝脏中占50%，在胆汁中占95%）。在水溶性部分发现了三种类型的代谢产物。一种类型对β-葡萄糖醛酸酶和芳基硫酸酯酶水解敏感，第二种类型对酶水解不敏感但对酸水解敏感，第三种类型对酶水解和酸水解均不敏感。通过反相高效液相色谱法分析脂溶性化合物和对酶水解敏感的结合物，发现它们包含多种代谢产物。本研究表明，肝脏摄取地高辛后会迅速且广泛地代谢为高极性代谢产物，并迅速排泄到胆汁中。
