给药途径及杞归八味口服液对大鼠二苯乙烯苷药代动力学的影响

Effects of Administration Routes and Qiguibawei Oral Liquid on the Pharmacokinetics of Stilbene Glucoside in Rats

目的考察不同给药途径及中药复方杞归八味口服液对二苯乙烯苷药代动力学的影响。方法将15只SD大鼠随机分为A组(60 mg/kg二苯乙烯苷、腹腔注射)、B组(60 mg/kg二苯乙烯苷、灌胃)、C组[杞归八味口服液(相当于60 mg/kg二苯乙烯苷)、灌胃],各5只。3组大鼠分别于不同时间点剪尾取血,采用高效液相色谱法检测血药浓度。结果A组、B组大鼠的药代动力学过程均符合血管外给药二室模型;A组、B组大鼠给药后能快速进入体循环,2 min即能在血液中检测到药物,平均达峰时间(t_(max))分别为(9.00±4.18)min和(14.00±5.48)min;B组大鼠给药后峰浓度(Cmax)和药时曲线下面积(AUC0-∞)分别为(0.44±0.40)mg/L和(6.04±6.68)mg·min/L,显著低于A组的(23.79±7.12)mg/L和(435.89±75.69)mg·min/L(P<0.05);B组大鼠的相对生物利用度为1.39%;C组大鼠二苯乙烯苷的血药浓度低于检测限(0.025 mg/L)。结论口服二苯乙烯苷的生物利用度极低,而杞归八味口服液能使其生物利用度进一步降低。

Objective To investigate the effects of different administration routes and traditional Chinese medicine compound(Qiguibawei Oral Liquid)on the pharmacokinetics of stilbene glucoside.Methods A total of 15 SD rats were randomly divided into group A(60 mg/kg of stilbene glucoside,intraperitoneal injection),group B(60 mg/kg of stilbene glucoside,intragastric administration),group C[Qiguibawei Oral Liquid(equivalent to 60 mg/kg of stilbene glucoside,intragastric administration),five rats in each group.The blood samples were collected by cutting tail of rats in the three groups at different time points,and the blood concentration was detected by the high-performance liquid chromatography(HPLC).Results The pharmacokinetic process of the rats in the groups A and B was consistent with the two-compartment model of extravascular administration.After administration,stilbene glycoside could enter the systemic circulation quickly and be detected in the blood within 2 min in group A and group B,and the mean time to peak(t_(max))was(9.00±4.18)min and(14.00±5.48)min,respectively.The maximum concentration(Cmax)and the area under the drug time curve(AUC0-∞)in group B were(0.44±0.40)mg/L and(6.04±6.68)mg·min/L,which were significantly lower than(23.79±7.12)mg/L and(435.89±75.69)mg·min/L in group A.The relative bioavailability in group B was 1.39%,and the plasma concentration of stilbene glucoside in group C was lower than the limit of detection(0.025 mg/L).Conclusion The bioavailability of oral administration of stilbene glucoside is very low,and Qiguibawei Oral Liquid further reduces its bioavailability.