Excretion of Berberine and Its Metabolites in Oral Administration in Rats
Excretion of Berberine and Its Metabolites in Oral Administration in Rats
复制标题
大鼠口服小檗碱及其代谢物的排泄
DOI：
10.1002/jps.23718
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发表时间：
2013-11-01
影响因子：
3.8
通讯作者：
Jiang, Jian-Dong
中科院分区：
文献类型：
--
作者：
Ma, Jing-Yi;Feng, Ru;Jiang, Jian-Dong
小檗碱（BBR）在临床上被证实具有广泛的治疗糖尿病和高胆固醇血症的生物活性。然而，很少有药代动力学研究来阐明BBR及其代谢产物的排泄。本实验研究了BBR及其代谢产物在大鼠体内的排泄情况。采用液相色谱-离子阱飞行时间质谱法检测胆汁、尿液和粪便中的代谢物;同时，开发了经验证的液相色谱-串联质谱法对其进行定量。体内给药后，鉴别并澄清了16种代谢产物，包括10种I相代谢产物和6种II相代谢产物。BBR的总回收率为22.83%（原型19.07%，代谢产物3.76%），胆汁（24 h）、尿液（48 h）和粪便（48 h）中BBR的回收率分别为9.2 × 10 ~（-6）%、0.0939%和22.74%。83%的BBR以沙利芬定（M1）的形式从胆汁中排出，而沙利芬定（M1）和小檗红宾（M2）是主要代谢物，占尿液排泄量的78%。BBR及其代谢产物主要存在于粪便中，占原型的84%。总之，我们提供了大鼠体内经口给药后BBR及其代谢产物的排泄曲线。(c)2013 Wiley Periodicals，Inc.和American Pharmacologist Association J Pharm Sci 102：4181-4192，2013
Berberine (BBR) has been confirmed to show extensive bioactivities for the treatments of diabetes and hypercholesterolemia in clinic. However, there are few pharmacokinetic studies to elucidate the excretions of BBR and its metabolites. Our research studied the excretions of BBR and its metabolites in rats after oral administration (200mg/kg). Metabolites in bile, urine, and feces were detected by liquid chromatography coupled to ion trap time-of-flight mass spectrometry; meanwhile, a validated liquid chromatography coupled with tandem mass spectrometry method was developed for their quantifications. Sixteen metabolites, including 10 Phase I and six Phase II metabolites were identified and clarified after dosing in vivo. Total recovered rate of BBR was 22.83% (19.07% of prototype and 3.76% of its metabolites) with 9.2x10(-6)% in bile (24h), 0.0939% in urine (48h), and 22.74% in feces (48h), respectively. 83% of BBR was excreted as thalifendine (M1) from bile, whereas thalifendine (M1) and berberrubine (M2) were the major metabolites occupying 78% of urine excretion. Most of BBR and its metabolites were found in feces containing 84% of prototype. In summary, we provided excretion profiles of BBR and its metabolites after oral administration in rats in vivo. (c) 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:4181-4192, 2013