陈皮水溶性总生物碱的升血压作用量-效关系及药动学研究

 目的:研究陈皮水溶性生物碱iv给药后对大鼠的升血压作用，探讨其量-效关系，并测算主要药动学参数。方法:将陈皮水溶性生物碱按含生药童1 000 mg·kg^-1的剂量给大鼠iv后，记录不同时刻的动脉收缩压(SAP)、舒张压(DAP)及心率(HR)，计算平均动脉压(MAP)及其净增百分率(E%)。大鼠按1 000,500,250 mg·kg^-1的剂量给药后，以MAP的总平均上升百分率为药效指标，测算量-效、时-效关系，计算药动学参数K等。结果:陈皮水溶性生物碱可显著升高大鼠的血压，SAP的最大平均上升百分率平均达53%，维持升压4 min；心率在给药后20s内明显减少(P<0.05),2 min后则显著增加(P<0.05～0.001),9 min后恢复正常；大鼠的MAP平均上升百分率与上述3剂量的对数剂量间呈良好的线性关来(r=0.998 5)，给药后0.5～5 min动物体内残余药量呈一级消除，经计算求出其药动学参数K=0.55min^-1, t_1/2=1.24min。结论:陈皮水溶性生物碱对大鼠有明显的升血压作用，且在一定剂量范围内量-效、时-效呈线性相关，其作用时间短哲，清除快。

The rising BP effect of Chenpi's TSA and its dose-response relationship and pharmacokinetics

OBJECTIVE:To study the rising BP(blood pressure)effects of total soluble alkaloid(TSA)，which was extracted from a Chinese medical herb-Chenpi(Pericarpium Citri Reticulatae)，and its ose-response relationship and pharmacokinetics. METHODS: Given iv the TSA with 1 000 mg herbs·kg^-1 in rats, we recorded the SAP, DAP and HR, calculated the MAP and its increased percentage. After rats were given iv TSA with 1 000, 500, 250 mg·kg^-1,the total percentage of MAP increased. The dose-response relationship and the pharmacokinetical data K, t_1/2(ED)，etc. were calculated. RESULTS: TSA elevated the BP of rats significantly, with a maximal SAP increasing precentage of over 53%. The BP restored 5 minutes later. The HR of rats decreased visibly in the first 20s(P<0.05)，but 2 minutes later, it increased significantly(P<0.05～0.001)and restored after 10 minutes. The dose-response relationship was linear( r=0.998 5).After given iv TSA 0.5 to 5 minutes, the drug was eliminated at I stage. The pharmacokinetical data K was about 0.55 minute^-1，t_1/2(ED) abut 1.24 minutes. CONCLUSION: TSA can elevate the BP of rats immediately. Its dose-response and time-response is in linear relationship. Its actions are short, and elimination is so fast.