莪术对甲氨蝶呤在正常和气滞血瘀大鼠体内药动学的影响

Effect of Curcumae Rhizoma on the pharmacokinetics of methotrexate in normal and blood stasis rats.

目的探讨莪术对正常和气滞血瘀大鼠体内甲氨蝶呤(MTX)药动学的影响,为临床合理用药提供依据。方法采用束缚和冰水浴2周构建大鼠气滞血瘀模型。将正常大鼠和气滞血瘀大鼠各分成单用组(MTX 5.17 mg/kg)和联合用药组(MTX 5.17 mg/kg,醋莪术0.93 g/kg),灌胃给药,于不同时间点进行眼眶静脉丛采血500μL/次,固相萃取(SPE)法处理血浆后用HPLC法进行分析,DAS2.0软件非隔室模型估算药动学参数。结果除Tmax外,正常组与模型组主要药动学参数差异均无统计学意义;联合用药组与单用组比较,AUC_(0-t)、AUC_(0-∞)、C_(max)均表现出增大趋势。结论血瘀模型对甲氨蝶呤药动学无显著影响;模型和正常情况下,莪术均可促进MTX吸收,两者合用时应减少MTX剂量并关注MTX毒副反应。

Objective To study the effect of Curcumae Rhizoma on the pharmacokinetics of methotrexate in normal and blood stasis rats to provide a basis for clinical rational use of drugs.Methods The method of bondage and ice water bath were applied to establish the blood stasis rat model.The normal and blood stasis rats were divided into methotrexate group（ 5.17 mg/kg） and combination group（ methotrexate 5.17 mg/kg combined with Curcumae Rhizoma 0.93 g/kg） respectively.After intragastric administration,the blood was collected from orbit venousplexus at different interval.Serum samples were prepared by solid phase extraction（ SPE） method, and the drug concentration was determined by HPLC method.The data were analyzed by pharmacokinetic software DAS（ 2.1） with non-compartment modal.Results Except for Tmax,other pharmacokinetic parameters of the normal groups had no statistical difference with model groups.Compared with the methotrexate groups, AUC0-t、AUC0-∞、Cmax was increased in combination groups.Conclusion Blood stasis model had no significant effects on the pharmacokinetics parameter of methotrexate.Curcumae Rhizoma could promote the absorption of methotrexate both in normal and model state,indicating that the dose of methotrexate should be reduced when combined with Curcumae Rhizoma.