二甲双胍-白藜芦醇复合物油包水型纳米乳在体肠吸收及其药代动力学研究

陈云; 曾梅; 徐靖鑫; 胡娟; 张景勍

doi:10.11665/j.issn.1000-5048.20210309

二甲双胍-白藜芦醇复合物油包水型纳米乳在体肠吸收及其药代动力学研究

1.
重庆医科大学药学院重庆高校药物工程研究中心，重庆 400016
2.
重庆华邦制药有限公司，重庆 401121

基金项目: 重庆市社会事业与民生保障科技创新专项资助项目 (No.cstc2017shmsA130028）

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出版历程
- 收稿日期: 2021-01-27
- 修回日期: 2021-05-10
- 刊出日期: 2021-06-24

In situ intestinal absorption and pharmacokinetic study of metformin-resveratrol compound water-in-oil nanoemulsion

1.
Chongqing Research Center for Pharmaceutical Engineering, College of Pharmacy, Chongqing Medical University, Chongqing 400016
2.
Chongqing Huapont Pharm Co., Ltd, Chongqing 401121, China

Funds: This study was supported by Chongqing Science and Technology Innovation Project for Social Undertakings and Livelihood Security (No.cstc2017shmsA130028)

摘要

摘要: 考察二甲双胍-白藜芦醇复合物油包水型纳米乳（metformin-resveratrol compound water-in-oil nanoemulsion，MRCE）在大鼠体内的在体肠吸收特性和药代动力学行为。通过构建大鼠在体肠单向灌流模型，研究MRCE在不同肠段的吸收情况，大鼠被随机分为两组，二甲双胍和MRCE灌胃给药后，在预设时间点取血，HPLC法测定肠灌流样品和各时间点血样中二甲双胍的含量，绘制血药浓度-时间曲线，DAS 2.1.1软件处理并分析药代动力学数据。MRCE在各肠段的吸收速率常数（K_a）、有效渗透率（P_eff）和吸收百分率（PA）均显著高于二甲双胍（P < 0.05）；MRCE的血药浓度-时间曲线下面积（AUC_{0-72 h}）、半衰期（t_1/2）和平均滞留时间（MRT_{0-72 h}）分别为二甲双胍的1.68、11.25和6.97倍（P < 0.01）。MRCE的相对生物利用度为167.6%。MRCE的AUC_{0-72 h}的90%可置信区间为156.9%~187.4%，不在生物等效性标准区间内。MRCE肠道吸收情况明显优于游离二甲双胍；结果表明，MRCE提高了二甲双胍的口服生物利用度，且与二甲双胍生物不等效。
- 二甲双胍 /
- 白藜芦醇 /
- 复合物 /
- 纳米乳 /
- 肠道吸收 /
- 药代动力学 /
- 生物利用度
Abstract: To investigate the in situ intestinal absorption characteristics and pharmacokinetic behavior of metformin-resveratrol compound water-in-oil nanoemulsion (MRCE) in rats, the in situ intestinal perfusion model was constructed in rats to study the intestinal absorption characteristics of MRCE in different intestinal segments. Male Sprague-Dawley rats were randomly divided into two groups. After intragastric administration of metformin and MRCE, blood was taken at a preset time point. The content of metformin in intestinal perfusion samples and blood samples at various time points was determined by HPLC. Plasma concentration-time profiles of free metformin and MRCE were calculated, and the main pharmacokinetic data were processed and analyzed by DAS 2.1.1 software. The absorption rate constant (K_a), the effective permeability (P_eff) and the percentage of absorption (PA) of MRCE in each intestinal segment were significantly higher than those of metformin (P < 0.05). The area under the drug-time curve (AUC_{0-72 h}), the half-life (t_1/2) and mean residence time (MRT_{0-72 h}) of MRCE were 1.68, 11.25 and 6.97 times of metformin, respectively (P < 0.01).The relative bioavailability of MRCE was 167.6%. The 90% confidence interval of AUC_{0-72 h} was 156.9%-187.4%, which was not within the standard interval of bioequivalence. The intestinal absorption of MRCE was significantly better than that of free metformin; MRCE improved the oral bioavailability of metformin and was not bioequivalent to metformin.
- metformin /
- resveratrol /
- compound /
- nanoemulsion /
- intestinal absorption /
- pharmacokinetics /
- bioavailability

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