在体皮肤微透析法研究制川乌白芍配伍对6种酯型生物碱局部药动学的影响

Effects of combined administration of Paeoniae Radix Alba on local pharmacokinetics of six aconite alkaloids by skin microdialysis in vivo

以小鼠为实验对象,分别给予制川乌凝胶和制川乌-白芍凝胶,生理盐水为灌流液,灌流速度2μL·min-1,每30 min收集1次,共收集8 h。采用HPLC-MS/MS测定制川乌中6种生物碱的含量,并绘制浓度-时间曲线,计算药动学参数并对其参数进行SPSS分析,研究制川乌白芍配伍对制川乌中6种生物碱透皮吸收的影响。结果显示制川乌白芍配伍后,3种单酯型生物碱达峰时间Tmax缩短,同时,苯甲酰乌头原碱和苯甲酰次乌头原碱的Cmax和AUC均增加;而配伍后,3种双酯型生物碱的AUC均降低,且次乌头碱的Tmax延长,Cmax降低。结果表明制川乌白芍配伍促进了单酯型生物碱的经皮渗透,抑制了部分双酯型生物碱的吸收,该研究从经皮转运的角度阐明了制川乌-白芍伍用"增效减毒"的配伍机制,同时也为其他药对配伍机制的研究提供参考。

The Aconiti Radix Cocta gel and Aconiti Radix Cocta combined with Paeoniae Radix Alba gel were administered to mice.Physiological saline was taken as perfusate. The perfusion rate was 2 μL·min-1and the microdialysis samples were collected every0. 5 h intervals for eight times. The six aconitine alkaloids concentration in perfusate were determined by HPLC-MS / MS. The concentration-time curves were plotted,and the pharmacokinetic parameters were calculated and analyzed by SPSS. The effects of Paeoniae Radix Alba on transdermal permeation role of six aconitine alkaloids in herb couple of Paeoniae Radix Alba-Aconiti Radix Cocta were investigated. According to the results,Tmaxof the three mono-ester aconitum alkaloids of Aconiti Radix Cocta combined with Paeoniae Radix Alba groups were shortened,meanwhile,Cmaxand AUC of benzoylaconine and benzoylhypaconine were increased. However,AUC of the three diester-type alkaloids were reduced,with Tmaxof hypaconitine prolonged and Cmaxlowered. The study suggested that the combined administration of Aconiti Radix Cocta and Paeoniae Radix Alba promoted the transdermal permeation of mono-ester aconitum alkaloids,and inhibited the absorption of parts of diester-type alkaloids. This study proved the decreasing toxicity and increasing efficacy of the combination of Aconiti Radix Cocta and Paeoniae Radix Alba on the transdermal permeation,and provided a reference for studies on the prescription combination regularity and relevant practices.