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.
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.
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.