| 摘要: |
| 目的 考察吴茱萸碱油包水型复合纳米乳在雄性SD大鼠体内的药代动力学、在体肠吸收情况。方法 12只雄性SD大鼠灌胃给予吴茱萸碱油包水型复合纳米乳和吴茱萸碱（吴茱萸碱质量浓度为100 mg/kg）后，分别于0.083、0.25、0.5、0.75、1、2、5、8、12、24、48和72 h时眼底采血，用HPLC法检测血药浓度，用DAS 2.1.1软件对数据进行拟合，分析其药动学行为；建立在体单向肠灌流模型，研究药物在大鼠体内的吸收情况。结果 吴茱萸碱油包水型复合纳米乳的药时曲线下面积（AUC）为（4 924.59±1 105.28）μg·L·h-1，峰浓度（Cmax）为（305.47±51.23）μg·L-1和达峰时间（Tmax）为（0.83±0.29）h；其在胃中的吸收速率常数（Ka）为（1.05±0.82）×10-5 L·s-1；在十二指肠、空肠、回肠和结肠中的Ka分别为（12.19±1.57）×10-5、（12.66±1.35）×10-5、（11.94±4.17）×10-5和（11.21±1.25）×10-5 L·s-1，有效渗透系数（Peff）分别为（26.03±3.84）×10-5、（18.48±5.99）×10-5、（19.77±2.59）×10-5和（36.02±1.48）×10-5 cm·s-1。结论 吴茱萸碱油包水型复合纳米乳增强了吴茱萸碱在胃和各个肠段中的吸收，提高了吴茱萸碱在大鼠体内的生物利用度。 |
| 关键词: 吴茱萸碱 纳米乳 药代动力学 肠吸收 单向肠灌流 |
| DOI：10.16781/j.0258-879x.2017.02.0249 |
| 投稿时间：2016-06-22修订日期：2016-09-02 |
| 基金项目:重庆市科委项目（cstc2015jcyjBX0027）. |
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| Pharmacokinetics and in situ intestinal absorption of evodiamine complex water-in-oil nanoemulation |
| YAN Sheng-lei1,HU Jiang-bo2,WANG Xue1,SHI Ming-xin1,ZHANG Jing-qing1* |
(1. Chongqing Research Center for Pharmaceutical Engineering, Chongqing Medical University, Chongqing 400016, China;
2. Department of Pharmacy, Chongqing Nan'an Maternal and Child Health Care Hospital, Chongqing 400060, China
*Corresponding author) |
| Abstract: |
| Objective To investigate the pharmacokinetic behavior and in situ intestinal absorption of evodiamine complex water-in-oil nanoemulation (WECNE). Methods WECNE was formulated with the titration stirring methods. Twelve male SD rats were intragastrically administered with evodiamine (EDA) and WECNE at the same EDA dose of 100 mg·kg-1. Blood samples were collected from eye socket at 0.083, 0.25, 0.5, 0.75, 1, 2, 5, 8, 12, 24, 48 and 72 h after intragastrical administration, and the plasma concentrations of EDA were determined by RP-HPLC. DAS 2.1.1 software was applied to evaluate the pharmacokinetic behavior. Single-pass intestinal perfusion was carried out to test the intestinal absorption in situ. Results The area under the curve (AUC0-72 h), peak concentration (Cmax) and time to peak (Tmax) of WECNE were (4 924.59±1 105.28) μg·L·h-1, (305.47±51.23) μg·L-1 and (0.83±0.29) h, respectively. The absorption rate constant (Ka) of WECNE in the stomach, duodenum, jejunum, ileum and colon were (1.05±0.82)×10-5, (12.19±1.57)×10-5, (12.66±1.35)×10-5, (11.94±4.17)×10-5 and (11.21±1.25)×10-5 L·s-1, respectively. In addition, the effective permeability (Peff) of WECNE in the duodenum, jejunum, ileum and colon were (26.03±3.84)×10-5, (18.48±5.99)×10-5, (19.77±2.59)×10-5 and (36.02±1.48)×10-5 cm·s-1, respectively. Conclusion WECNE can improve the bioavailability and the absorption in situ of EDA in different parts of the gastrointestinal tract. |
| Key words: evodiamine nanoemulation pharmacokinetics intestinal absorption single-pass intestinal perfusion |
