脱氢卡维丁大鼠在体肠吸收与体外经β-葡萄糖醛酸苷酶代谢的研究  

Assessment of the intestinal absorption andβ-glucuronidase metabolism profiles of Dehydrocavitin in situ and in vitro

作　　者：郭妍如 梁中旭 温成铭 罗君 赵琳珺 蒋学华[2] 王凌[2] GUO Yanru;LIANG Zhongxu;WEN Chengming;LUO Jun;ZHAO Linjun;JIANG Xuehua;WANG Ling*(Guizhou University of Traditional Chinese Medicine,Guiyang,Guizhou,550002 P.R.China;West China School of Pharmacy,Sichuan University,Chengdu,Sichuan,610041 P.R.China;the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang,Guizhou,550001 P.R.China;Puding County Hospital of Traditional Chinese Medicine,Anshun,Guizhou,562100 P.R.China;Xintian Community Health Service Center,Wudang District,Guiyang,Guizhou,550001 P.R.China)

机构地区：[1]贵州中医药大学,贵州贵阳550002 [2]四川大学华西药学院,四川成都610041 [3]贵州中医药大学第一附属医院,贵州贵阳550001 [4]普定县中医医院,贵州安顺562100 [5]贵阳市乌当区新天社区卫生服务中心,贵州贵阳550001

出　　处：《华西药学杂志》2023年第4期389-393,共5页West China Journal of Pharmaceutical Sciences

基　　金：贵州省科学技术厅中央引导地方基金(黔科中引地[2020]4001号);贵州省卫生健康委科学技术基金(gawkj2021-462)。

摘　　要：目的评价脱氢卡维丁的大鼠在体肠吸收与经β-葡萄糖醛酸苷酶(GUS)的代谢特性。方法采用LC-MS/MS法检测脱氢卡维丁的含量,并进行方法学验证;采用大鼠单向肠灌注模型研究脱氢卡维丁的在体肠吸收,以体外代谢法研究其经GUS的代谢行为。结果所用方法专属性强、结果准确、精密度高,1~100 ng·mL^(-1)脱氢卡维丁与峰面积的线性关系良好(r=0.9966)。脱氢卡维丁在大鼠的不同肠段均有吸收,其中,十二指肠与空肠的吸收速率常数(K_(a))和有效渗透系数(P_(eff))均高于回肠与结肠,但两个肠段间的差异均无统计学意义。此外,在十二指肠与空肠段,脱氢卡维丁中、高浓度组的K_(a)、P_(eff)相较于低浓度组有一定下降,且差异具有统计学意义。脱氢卡维丁经GUS代谢的K_(m)为10.3±1.63μg·mL^(-1),Vmax为8.325±0.524 ng·mL^(-1)·min-1/KU GUS。结论脱氢卡维丁主要在大鼠十二指肠与空肠被吸收,其次是回肠,结肠吸收最少。吸收机制以被动扩散为主,但在十二指肠与空肠部位的吸收可能同时存在主动转运过程;脱氢卡维丁可经GUS代谢,该过程可能会影响其在机体中的吸收。OBJECTIVE To assess the in situ intestinal absorption and in vitroβ-glucuronidase(GUS)metabolism profiles of Dehydrocavitin(DHC)in rats.METHODS A HPLC-MS/MS method was developed and validated to determine DHC concentration.DHC in situ intestinal absorption and in vitro GUS metabolism were evaluated by a single-pass intestinal perfusion model and GUS-mediated in vitro metabolism system.RESULTS The methods validation results showed that the established DHC determination method was specific,sensitive,and accurate with a good linearity within 1-100 ng·mL^(-1),and the correlation coefficient was 0.9966.The in-situ data indicated that DHC could be absorbed in the whole intestinal of rats.Indeed,the K_(a)and P_(eff)in the duodenum and jejunum were higher than in the ileum and colon.However,K_(a)and P_(eff)showed no significant difference between the duodenum and jejunum.Besides,the K_(a)and P_(eff)in the medium and high concentration group of DHC were decreased compared with the low concentration group in both duodenum and jejunum.Conversely,DHC K_(m)and Vmax of GUS-mediated metabolism were 10.3±1.63μg·mL^(-1)and 8.325±0.524 ng·mL^(-1)·min-1/KU GUS,respectively.CONCLUSION DHC is mainly absorbed in the rat's duodenum and jejunum,followed by the ileum colon the least.Passive diffusion is the primary absorption mechanism.However,active transport may play a role in DHC absorption in rat's duodenal and jejunal.DHC is well metabolized by GUS,which may affect its intestinal absorption.

关 键 词：脱氢卡维丁 岩黄连 肠吸收 肠道代谢 Β-葡萄糖醛酸苷酶 高效液相色谱串联质谱 单向肠灌注 体外代谢 

分 类 号：R917[医药卫生—药物分析学]