去氢骆驼蓬碱衍生物DH-004大鼠在体肠吸收动力学研究  

Study on the absorption kinetics of harmine derivative DH-004 in rat intestine

作　　者：李玉玲 高惠静[2] 冉鑫 马桂芝[1] 滕亮[2] LI Yu-ling;GAO Hui-jing;RAN Xin;MA Gui-zhi;TENG Liang(College of Pharmacy,Xinjiang Medical University,Urumqi 830011,Xinjiang Uygur Autonomous Region,China;State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia,Department of Pharmacy,The First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,Xinjiang Uygur Autonomous Region,China)

机构地区：[1]新疆医科大学药学院,新疆维吾尔自治区乌鲁木齐830011 [2]新疆医科大学第一附属医院药学部省部共建中亚高发病成因与防治国家重点实验室,新疆维吾尔自治区乌鲁木齐830054

出　　处：《中国临床药理学杂志》2021年第7期878-882,共5页The Chinese Journal of Clinical Pharmacology

基　　金：中华医学会临床药学分会吴阶平医学基金会科研专项基金资助项目(320.6750.19090-9)。

摘　　要：目的考察去氢骆驼蓬碱衍生物DH-004大鼠在体肠吸收动力学特征,探讨其可能的吸收机制。方法建立UPLC法测定灌流液中DH-004浓度,用大鼠在体单向肠灌流模型考察不同质量浓度的DH-004在不同肠段的吸收特征。结果 DH-004在全肠段均有吸收。20.0μg·mL^(-1) DH-004在十二指肠、空肠、回肠和结肠的吸收速率常数(K_a)分别为(11.66±3.84)×10^(-2),(10.85±2.65)×10^(-2),(7.48±1.70)×10^(-2)和(4.75±1.14)×10^(-2) min,药物表观渗透系数(P_(app))分别为(1.47±0.33)×10^(-2),(1.55±0.20)×10^(-2),(1.25±0.10)×10^(-2)和(0.98±0.22)×10^(-2) cm·min^(-1)。DH-004在十二指肠段与空肠段的K_a均明显大于其在回肠和结肠的K_a(均P<0.05)。结论 DH-004在大鼠小肠全段有不同程度地吸收,十二指肠和空肠可能为其主要吸收部位。Objective To investigate the absorption characteristics of harmine derivative DH-004 in rat intestine and its possible absorption mechanism.Methods The concentration of DH-004 in perfusion solution was determined by UPLC,and in situ rats single pass perfusion model was used to investigate the absorption characteristics of different concentrations of DH-004 in different intestinal segments.Results DH-004 can be absorbed in all intestinal segments of rats.The absorption rate constants(Ka)of DH-00420.0μg·mL^(-1) in duodenum,jejunum,ileum and colon were(11.66±3.84)×10^(-2),(10.85±2.65)×10^(-2),(7.48±1.70)×10^(-2) and(4.75±1.14)×10^(-2) min,separately.The apparent permeability coefficients(Papp)were(1.47±0.33)×10^(-2),(1.55±0.20)×10^(-2),(1.25±0.10)×10^(-2) and(0.98±0.22)×10^(-2) cm·min^(-1),separately.Ka of DH-004 in duodenum and jejunum were significantly higher than those in ileum and colon(all P<0.05)Conclusion DH-004 can be absorbed in all segments of the rat intestine with different degrees.The main absorption segments for DH-004 may be the duodenum and jejunum.

关 键 词：DH-004 去氢骆驼蓬碱衍生物 肠吸收 单向灌流法 UPLC 

分 类 号：R97[医药卫生—药品]