| 摘要: |
| 目的 研究环维黄杨星D（CB）羟丙基-β-环糊精包合物（CBHD）的大鼠在体肠吸收特征，探讨细胞色素P450抑制剂酮康唑（KET）对CB和CBHD肠吸收的影响。方法 雄性SD大鼠24只，随机平均分为4组：CB组、CBHD组、KET+CB组、KET+CBHD组，每组6只，建立大鼠在体肠吸收模型。采用单向灌流法考察CB和CBHD在大鼠各肠段的吸收情况，及KET对CB和CBHD肠吸收行为的影响。以高效液相色谱/荧光检测器（HPLC/FLD）法测定CB浓度，色谱柱为依利特C18柱（250 mm×4.6 mm，5 μm）；流动相为甲醇-水（85︰15，体积比）；激发波长为231 nm，发射波长为385 nm；柱温为25℃，流速为1.0 mL/min；进样量为20 μL。结果 所建HPLC/FLD法专属性好，以CB峰面积（A）对CB浓度（C）进行线性回归，建立的标准曲线方程为A=106.7 C+41.861（R2=0.999 08），表明CB在0.5～20.0 μg/mL范围内线性良好。低、中、高3个浓度（1.0、5.0、10.0 μg/mL）样品溶液的日内精密度分别为2.25%、2.44%、3.04%，日间精密度分别为4.22%、2.00%、2.50%，符合方法学要求。低、中、高浓度样品溶液的回收率分别为99.08%、98.24%、97.25%，符合方法学要求。加入KET后，CBHD在十二指肠、空肠、回肠、结肠的吸收速率常数（Ka）分别为CB的4.18、5.05、1.91、2.85倍（P<0.05），有效渗透率（Peff）分别为CB的4.92、5.98、2.19、3.24倍（P<0.05）。结论 KET可促进CB与CBHD在肠道的吸收。 |
| 关键词: 环维黄杨星D 包合物 酮康唑 肠吸收 |
| DOI：10.16781/j.0258-879x.2018.05.0568 |
| 投稿时间：2017-04-05修订日期：2017-08-26 |
| 基金项目:重庆市教育委员会科学技术研究资助项目 |
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| Ketoconazole promotes in situ intestinal absorption of cyclovirobuxine D hydroxypropyl-β-cyclodextrin inclusion complex in rats |
| LU Wen-juan,CHEN Jing,ZHANG Jing-qing,JIANG Xin-hui* |
(Chongqing Research Center for Pharmaceutical Engineering, Chongqing Medical University, Chongqing 400016, China
*Corresponding author) |
| Abstract: |
| Objective To study the in situ intestinal absorption characteristics of cyclovirobuxine D (CB) hydroxypropyl-β-cyclodextrin inclusion complex (CBHD) in rats, and to explore the effect of cytochrome P450 inhibitor ketoconazole (KET) on CB and CBHD in situ intestinal absorption. Methods Twenty-four male rats were randomized into CB, CBHD, KET+CB and KET+CBHD groups, with 6 rats in each group. In situ intestinal absorption was adopted in a rat model. One-way intestinal perfusion model was employed to investigate the absorption of CB and CBHD in the intestinal segments of rats and the effects of KET on CB and CBHD absorption. The concentration of CB was determined by highperformance liquid chromatography with fluorescence detector (HPLC/FLD; Lichrospher C18 column[250 mm×4.6 mm, 5 μm]). The mobile phase was methanol-water with volume ratio being 85︰15. The excitation wavelength was set at 231 nm, and emission wavelength was set at 385 nm. The column temperature was 25℃, and flow rate was 1.0 mL/min. The injection volume was 20 μL. Results The specificity of HPLC/FLD method was good and the standard curve equation was A=106.7 C+41.861 (R2=0.999 08) based on the linear regression of CB concentration (C) with CB peak area (A), indicating that the CB mass concentration was linear in the range of 0.5 to 20.0 μg/mL. The intra-day precision of the 1.0, 5.0 and 10.0 μg/mL samples was 2.25%, 2.44% and 3.04%, and the inter-day precision was 4.22%, 2.00% and 2.50%, respectively. The precision was good and the method was in accordance with the requirements of methodology. The recovery rates of the 1.0, 5.0 and 10.0 μg/mL samples were 99.08%, 98.24% and 97.25%, respectively, which were also in accordance with the requirements of methodology. The intestinal absorption rate constant (Ka) values of CBHD with KET were 4.18, 5.05, 1.91 and 2.85 times those of CB, and the effective permeability (Peff) values were 4.92, 5.98, 2.19 and 3.24 times those of CB in the duodenum, jejunum, ileum and colon, respectively (all P<0.05). Conclusion KET can improve the intestinal absorption of CB and CBHD in rats. |
| Key words: cyclovirobuxine D inclusion complex ketoconazole intestinal absorption |
