软坚散结方剂对大鼠体内5-氟尿嘧啶药代动力学行为的影响

Effect of Ruanjian Sanjie Prescription on Pharmacokinetic Behavior of 5-Fluorouracil in Rats

摘要:

目的: 考察软坚散结方剂对5-氟尿嘧啶大鼠体内药动学行为的影响. 方法: 大鼠单独注射5-氟尿嘧啶或联合灌胃给予软坚散结方剂,利用10%高氯酸溶液提取血浆中5-氟尿嘧啶,采用HPLC测定5-氟尿嘧啶含量,流动相0.01 mol·L^-1磷酸二氢钾水溶液,流速0.8 mL·min^-1,检测波长265 nm.运用WinNonlin 5.2.1软件以非房室模型法计算药动学参数. 结果: 在软坚散结方剂的干预下,5-氟尿嘧啶在大鼠体内血药浓度的达峰时间显著缩短,联用组和单用组分别为(0.381±0.075),(0.514±0.122) h;表观分布容积显著减少,2组分别为(5.915±1.196),(11.307±5.393) mL;2组的其他参数均未见显著性差异. 结论: 软坚散结方剂能促进大鼠体内5-氟尿嘧啶的吸收,抑制后者由血液向组织中分布.

Abstract:

Objective: To analysis effect of Ruanjian Sanjie (RJ) prescription on pharmacokinetic behavior of 5-fluorouracil (5-Fu) in rats. Method: Rats were divided into two groups,one group was given 5-Fu only and the other one was given 5-Fu and RJ prescription together.Plasma samples were separated and extracted by 10% perchloric acid solution,HPLC was employed to determine the content of 5-Fu with mobile phase of 0.01 mol·L^-1 potassium dihydrogen phosphate,a flow rate of 0.8 mL·min^-1 and detection wavelength at 265 nm.Pharmacokinetic parameters were calculated by WinNonlin 5.2.1 software with non-compartmental model. Result: RJ prescription could obviously reduce T_max [the combined group was (0.381±0.075) h and the single group was (0.514±0.122) h] and apparent volume of distribution [the combined group was (5.915±1.196) mL and the single group was (11.307±5.393) mL] of 5-Fu in rats,but no obvious changes on other parameters. Conclusion: RJ prescription can promote absorption of 5-Fu in rats by intraperitoneal injection,while inhibiting trend of 5-Fu distribution from blood to tissues.