银屑灵2号方对甲氨蝶呤大鼠体内药物动力学的影响  

Influence of Yinxieling Recipe 2 on Pharmacokinetics of Methotrexate in Rats

作　　者：李杨[1] 赵亚 卢传坚[1,2] 赵瑞芝[1,2] 

机构地区：[1]广州中医药大学第二临床医学院,广东广州510405 [2]广东省中医药科学院,广东广州510006

出　　处：《中药新药与临床药理》2015年第5期655-657,694,共4页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：广东省自然科学基金团队项目(S2013030011515);广东省中医院项目(YK2013B1N11);广东省产学研项目(2013 B090700015)

摘　　要：目的 探讨银屑灵2号对甲氨蝶呤（MTX）药物动力学的影响。方法 将12只SD大鼠随机分为MTX组（6 mg·kg-1）和联合用药组（MTX 6 mg·kg-1,银屑灵2号30 g·kg-1）,灌胃给药。于不同时间点进行眼眶静脉丛采血,固相萃取（SPE）法处理血浆后用HPLC法进行分析。色谱条件：Diamonsil C18（2）色谱柱;甲醇-0.1%甲酸水梯度洗脱;柱温：27℃,流速：1 m L·min-1;检测波长：302 nm;进样量：10μL。非隔室模型估算药代动力学参数。结果 MTX在0.052∽5.006 mg·L-1线性关系良好（r=0.9996）;检测限0.052 mg·L-1;提取回收率68%∽74%。与MTX组比较,联合用药组MTX清除延迟,Cmax增加1.106倍,AUC0-t增加0.898倍,AUC0-∞增加0.323倍。结论 银屑灵2号能够促进MTX吸收,延缓其消除,提高MTX的生物利用度,提示MTX与银屑灵2号方合用时,可能要减少MTX剂量。Objective To investigate the impact of Yinxieling Recipe 2 on the pharmacokinetics of methotrexate in rats after oral administration. Methods Twelve Sprague-Dawley rats were divided into methotrexate group （6 mg·kg-1） and combination group（methotrexate 6 mg· kg-1 combined with Yinxieling Recipe 2 30 g· kg-1）. At different time points after gastric gavage, blood was collected from orbit venous plexus, and serum samples were prepared by solid phase extraction（SPE） method, and then the drug concentration was determined by HPLC method. Chromatographic separation was achieved on a reversed-phase Diamonsil Cts（2） column with the mobile phase of methanol- formic acid water solution （0.1% formic acid） by gradient elution; the column temperature was 27 ℃ ; the flow rate was 1 mL·min-1; the detection wavelength was 302 nm, and the injection volume was 10μL. The results were analyzed by pharmacokinetic software DAS （2. I ） with non-compartment model. Results The linearity of the calibration curve was good in the range of 0.052-5.006 mg·L-1 for methotrexate （r=0.9996）, and the detection limit for methotrexate was 0.052 mg·L-1. The extract recoveries were from 68 % to 74 %. Compared with methotrexate group, the clearance of methotrexate was delayed in the combination group, Cmax was increased by 1.106 time, AUG 0-t） by 0.898 times, and AUG 0-∞ by 0.323 times. Conclusion Yinxieling Recipe 2 could enhance the bioavailability of methotrexate in rats by promoting the absorbance and delaying the clearance of methotrexate, indicating that when used together with methotrexate, the dose of methotrexate should be reduced.

关 键 词：甲氨蝶呤 银屑灵2号 相互作用 药代动力学 

分 类 号：R285.5[医药卫生—中药学]