Zhang Shuang-Qing, Zhang Shi-Zhong
Department of Nutrition and Metabolism, National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, 27 Nanwei Rd, Beijing, 100050, China.
Department of Physiology, Medical Science College, China Three Gorges University, 8 University Rd, Yichang, 443002, China.
Drug Test Anal. 2017 Oct;9(10):1604-1610. doi: 10.1002/dta.2188. Epub 2017 May 15.
Icaritin (ICT) displays numerous pharmacological activities for the treatment of various cancers, osteoporosis, inflammation, and angiocardiopathy. The absorption, distribution, metabolism, and excretion of ICT still remain unknown. ICT was administered to rats at 2 mg/kg for intravenous injection or 40 mg/kg for oral route. Major metabolite of ICT was identified using quadrupole time-of-flight (Q-TOF), and ICT and its major metabolite were quantified in plasma, tissues, urine, faeces, and bile by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). A total of 24 metabolites of ICT in plasma were identified and mono C-7 glucuronide glucuronidated icaritin (GICT) was the major metabolite of ICT after oral administration. The absolute bioavailability of ICT was 4.33% although ICT was rapidly absorbed into the blood. For oral administration, concentrations of GICT at various time points was 6.38-8.81-fold higher than those of ICT, and the area under the curve (AUC) of GICT was about 8-fold higher than that of ICT, while AUC values of ICT and GICT were almost equal for intravenous injection. Approximately 65.7% ICT and 42.7% GICT were distributed in liver and kidney, respectively. Unabsorbed ICT was mainly excreted as the parent form in faeces with at least 60% of administered dose during 24 h, whereas absorbed ICT was predominantly excreted as GICT from urine with 2.74% of administered dose accounting for 63.28% of absorbed drug. ICT was rapidly absorbed into the blood although a large amount of ICT remained unabsorbed, and then rapidly and mainly metabolized to GICT. ICT mainly distributed in liver, while GICT predominantly distributed in kidney. Absorbed ICT and GICT were predominantly excreted via urine, and unabsorbed ICT was mainly excreted as the parent form in faeces. Copyright © 2017 John Wiley & Sons, Ltd.
淫羊藿素（ICT）具有多种药理活性，可用于治疗多种癌症、骨质疏松症、炎症和心血管疾病。然而，ICT的吸收、分布、代谢和排泄情况仍不清楚。将ICT以2mg/kg的剂量静脉注射或40mg/kg的剂量口服给予大鼠。使用四极杆飞行时间质谱仪（Q-TOF）鉴定ICT的主要代谢产物，并通过超高效液相色谱-串联质谱法（UHPLC-MS/MS）对血浆、组织、尿液、粪便和胆汁中的ICT及其主要代谢产物进行定量。共鉴定出ICT在血浆中的24种代谢产物，单C-7葡萄糖醛酸化淫羊藿素（GICT）是口服给药后ICT的主要代谢产物。尽管ICT能迅速吸收入血，但其绝对生物利用度为4.33%。口服给药时，GICT在各个时间点的浓度比ICT高6.38-8.81倍，GICT的曲线下面积（AUC）约为ICT的8倍，而静脉注射时ICT和GICT的AUC值几乎相等。约65.7%的ICT和42.7%的GICT分别分布在肝脏和肾脏中。未吸收的ICT主要以原形经粪便排出，24小时内至少占给药剂量的60%，而吸收的ICT主要以GICT的形式经尿液排出，给药剂量的2.74%占吸收药物的63.28%。尽管大量ICT未被吸收，但ICT仍能迅速吸收入血，然后迅速且主要代谢为GICT。ICT主要分布在肝脏，而GICT主要分布在肾脏。吸收的ICT和GICT主要经尿液排出，未吸收的ICT主要以原形经粪便排出。版权所有©2017约翰威立父子有限公司。
