State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
J Pharm Sci. 2013 Nov;102(11):4181-92. doi: 10.1002/jps.23718. Epub 2013 Sep 4.
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 (200 mg/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 9.2 × 10(-6) % in bile (24 h), 0.0939% in urine (48 h), and 22.74% in feces (48 h), 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.
小檗碱（BBR）已被证实具有广泛的生物活性，可用于治疗糖尿病和高胆固醇血症。然而，目前很少有药代动力学研究来阐明 BBR 及其代谢物的排泄情况。我们的研究在大鼠体内口服（200mg/kg）后研究了 BBR 及其代谢物的排泄情况。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，建立了一种经验证的液相色谱-串联质谱法用于它们的定量分析。在体内给药后，共鉴定和阐明了 16 种代谢物，包括 10 种 I 相代谢物和 6 种 II 相代谢物。BBR 的总回收率为 22.83%（原型的 19.07%和代谢物的 3.76%），胆汁中回收率为 9.2×10(-6) %（24h），尿液中回收率为 0.0939%（48h），粪便中回收率为 22.74%（48h）。83%的 BBR 从胆汁中以他非伦定（M1）的形式排泄，而他非伦定（M1）和小檗红碱（M2）是尿液排泄的主要代谢物，占 78%。大部分 BBR 及其代谢物在粪便中发现，占原型的 84%。综上所述，我们提供了 BBR 及其代谢物在大鼠体内口服后的排泄谱。
