LC-MS/MS考察白芷香豆素成分对硫酸长春新碱肠道转运及药代动力学的影响

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

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LCMS/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）×10-6cm·s-1,三者与硫酸长春新碱的Papp[（0.227 2±0.014 8）×10-6cm·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。

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-tof 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 Cmaxwere（ 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.