Excretion of [3H] triptolide and its metabolites in rats after oral administration
Excretion of [3H] triptolide and its metabolites in rats after oral administration
复制标题
大鼠口服后[3H]雷公藤甲素及其代谢物的排泄
DOI：
10.1038/aps.2013.192
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发表时间：
2014-04-01
影响因子：
8.2
通讯作者：
Zhong, Da-fang
中科院分区：
文献类型：
--
作者：
Liu, Jia;Zhou, Xin;Zhong, Da-fang
目的：方法：Sprague道利大鼠单次灌胃给予[H-3]雷公藤甲素（0.8 mg/kg，100 μ Ci/kg）后，收集168 h尿、粪标本。为了研究胆汁排泄，通过胆管插管收集胆汁样品24小时。结果：未结扎胆管大鼠尿和粪便中总放射性回收率为86.6%~ 89.1%。经口给药后72 h内，大部分放射性（68.6%-72.0%）在粪便中回收，而尿液和胆汁中回收的放射性分别为17.1%-18.0%和39.0%-39.4%。HPLC/在线放射性色谱分析显示，大部分药物相关放射性以代谢产物的形式存在。此外，这些代谢产物的数量显着的性别差异被发现：单羟基雷公藤甲素硫酸酯是检测到的尿液，粪便和胆汁中的雌性大鼠的主要代谢产物，而只有微量的这些代谢产物被发现在雄性大鼠。结论：放射性标记的雷公藤甲素主要是在胆汁中分泌，并在粪便中消除。吸收的放射性主要以代谢物的形式消除，并且在回收的代谢物的量中观察到显著的性别差异，这可能是由磺基转移酶的性别特异性表达引起的。
Aim: To investigate the routes of elimination and excretion for triptolide recovered in rats.Methods: After a single oral administration of [H-3] triptolide (0.8 mg/kg, 100 mu Ci/kg) in Sprague Dawley rats, urine and fecal samples were collected for 168 h. To study biliary excretion, bile samples were collected for 24 h through bile duct cannulation. Radioactivity was measured using a liquid scintillation analyzer, and excretion pathway analysis was performed using an HPLC/on-line radioactivity detector.Results: The total radioactivity recovered from the urine and feces of rats without bile duct ligation ranged from 86.6%-89.1%. Most of the radioactivity (68.6%-72.0%) was recovered in the feces within 72 h after oral administration, while the radioactivity recovered in the urine and bile was 17.1%-18.0% and 39.0%-39.4%, respectively. The HPLC/on-line radiochromatographic analysis revealed that most of the drug-related radioactivity was in the form of metabolites. In addition, significant gender differences in the quantity of these metabolites were found: monohydroxytriptolide sulfates were the major metabolites detected in the urine, feces, and bile of female rats, while only traces of these metabolites were found in male rats.Conclusion: Radiolabeled triptolide is mainly secreted in bile and eliminated in feces. The absorbed radioactivity is primarily eliminated in the form of metabolites, and significant gender differences are observed in the quantity of recovered metabolites, which are likely caused by the gender-specific expression of sulfotransferases.