Effect of Coumarins from Angelicae Dahuricae Radix on Intestinal Transport Absorption and Pharmacokinetics of Vincristine Sulfate by LC-MS/MS

ZHU Jing-yun; GUAN Xue-jing; JIANG Qie-ying; ZHAO Guo-wei; LIAO Zheng-gen; LIANG Xin-li

doi:10.13422/j.cnki.syfjx.20180707

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Effect of Coumarins from Angelicae Dahuricae Radix on Intestinal Transport Absorption and Pharmacokinetics of Vincristine Sulfate by LC-MS/MS

更新时间：2024-01-04

- Effect of Coumarins from Angelicae Dahuricae Radix on Intestinal Transport Absorption and Pharmacokinetics of Vincristine Sulfate by LC-MS/MS
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 24, Issue 6, Pages: 82-88(2018)
- 作者机构：
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- DOI：10.13422/j.cnki.syfjx.20180707
  CLC： R285
- Published：2018
- 稿件说明：
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ZHU Jing-yun, GUAN Xue-jing, JIANG Qie-ying, et al. Effect of Coumarins from Angelicae Dahuricae Radix on Intestinal Transport Absorption and Pharmacokinetics of Vincristine Sulfate by LC-MS/MS[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(6): 82-88.
DOI：

ZHU Jing-yun, GUAN Xue-jing, JIANG Qie-ying, et al. Effect of Coumarins from Angelicae Dahuricae Radix on Intestinal Transport Absorption and Pharmacokinetics of Vincristine Sulfate by LC-MS/MS[J]. Chinese journal of experimental traditional medical formulae, 2018, 24(6): 82-88. DOI： 10.13422/j.cnki.syfjx.20180707.

摘要

目的：研究白芷香豆素类成分欧前胡素、异欧前胡素、氧化前胡素对硫酸长春新碱肠道转运及药代动力学的影响。方法：采用MDCK-MDR1细胞模型，考察欧前胡素、异欧前胡素、氧化前胡素对硫酸长春新碱肠道转运的影响。采用LC-MS/MS测定给药后不同时间血浆中药物浓度，研究欧前胡素、异欧前胡素、氧化前胡素成分对硫酸长春新碱药代动力学的影响。结果：长春新碱配伍质量浓度为10.80，5.42，1.35 mg ·L-1欧前胡素的表观渗透系数（Papp）分别为（0.287 2±0.026 6）×10-6，（0.351 5±0.041 6）×10-6，（0.294 9±0.006 8）×10-6 cm ·s-1，三者与硫酸长春新碱的Papp[（0.227 2±0.014 8）×10-6 cm ·s-1]比较有显著性差异（P<0.05）。硫酸长春新碱与欧前胡素、异欧前胡素、氧化前胡素配伍后药时曲线下峰面积（AUC0-t）分别为（343.50±10.29），（348.70±27.99），（235.70±17.56）μg ·h ·L-1，与硫酸长春新碱组比较有显著性差异（P<0.01）。药峰浓度（Cmax）分别为（81.870±8.517），（83.010±9.276），（60.440±6.679）μg ·L-1，与硫酸长春新碱组的比较有显著性差异（P<0.01）。结论：白芷香豆素类成分能促进硫酸长春新碱的肠道转运，提高其生物利用度。

Abstract

Objective: To investigate the influence of coumarins from Angelicae Dahuricae Radix

such as imperatorin

isoimperatorin and oxypeucedanin

on intestinal transport and pharmacokinetics of vincristine sulfate in rats.Method: MDCK-MDR1 cell model was used to investigate the effect of imperatorin

isoimperatorin and oxypeucedanin on intestinal transport of vincristine sulfate.The drug plasma concentration was determined by LC-MS/MS at different time

and the effect of coumarins from Angelicae Dahuricae Radix on the pharmacokinetics of vincristine sulfate was investigated.Result: The apparent permeability coefficient (Papp) of vincristine sulfate compatibility of 10.80

5.42

1.35 mg · L-1 of imperatorin were (0.287 2±0.026 6)×10-6

(0.351 5±0.041 6)×10-6

(0.294 9±0.006 8)×10-6 cm · s-1

they had significant difference (P<0.05) when compared with Papp=(0.227 2±0.014 8)×10-6 cm · s-1 of vincristine sulfate.AUC0-t of vincristine sulfate compatibility of imperatorin

isoimperatorin and oxypeucedanin were (343.50±10.29)

(348.70±27.99)

(235.70±17.56) μg · h · L-1

their Cmax were (81.87±8.517)

(83.01±9.276)

(60.44±6.679) μg · L-1;there were significant difference (P<0.01) when compared with the control group of vincristine sulfate.Conclusion: Coumarins from Angelicae Dahuricae Radix can promote the transport absorption of vincristine sulfate and improve its bioavailability.

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