香加皮配方颗粒在小鼠体内的毒代动力学研究

Study on Toxicokinetics of Cortex Periplocae Dispensing Granule in Mice

目的：研究香加皮配方颗粒毒性成分在小鼠体内的代谢。方法：Bliss测定小鼠灌胃和腹腔注射给药的LD50。另取小鼠预先腹腔注射预负荷7.00g生药/kg,分别于药后1、2、4、6、8、12、16、24h补予7.00g生药/kg,用死亡率法计算体内残存量和表观代谢参数。结果：香加皮配方颗粒小鼠灌胃的LD50（95%可信限）为89.11（85.44-92.44）g生药/kg,小鼠腹腔注射的LD50（95%可信限）为10.35（9.66-11.10）g生药/kg,口服生物利用度F=11.61%。香加皮配方颗粒体内残存量并不是随着时间而一直降低,在6、12h出现了两个高峰点,其后呈一级动力学消除,12h以后消除相的消除半衰期t1/2=7.55h,消除速度常数K=0.0918/h。结论：香加皮配方颗粒的毒性成分代谢过程较复杂,可能存在肠肝循环或毒性代谢产物生成。

Objective ：To study metabolism of toxic components of Cortex Periplocae Dispensing Granule（CPDG） in mice. Methods： Mice were intragastrically and intraperitoneal treated with CPDG and LD50 was measured by Bliss. Others mice had repeated administration at the 1 st ,2nd,4th,6th,8th, 12th, 16th,24th hour after intraperitoneal treated with CPDG 7.00g herbs/kg. Apparent pharmacokinetic parameters and body burden were determinated by acute mortality of mice. Results： LD50 （95% confidence interval） was 89.11 （ 85.44 - 92.44） g herbs/kg by intragastrically administration and LD50 （ 95 % confidence interval） by intraperitoneal administration was 10.35 （9.66 - 11.10）g herbs/kg. The oral bioavailability was 11.61%. Body burden was decreased all along and there were two peak in 6h and 12h. Elimation phase exhibited first - order kinetic elimination after 12h. Elimination half life（t1/2） was 7.55h and elimination rate constant （K） was 0. 0918/h. Conclusion ： Metabolic process of toxic components of CPDG was complex. During the time, there probably was enterohepatic circulation and toxic metabolite was produced.