中药诃子的主要成分没食子酸在异育银鲫体内药物代谢动力学研究

在(20±1)℃的水温条件下,以77 mg/kg的单剂量,给异育银鲫(Carassius auratus gibelio)口灌诃子(Fructus chebulae)水剂,以诃子中的主要成分没食子酸为检测目标,用高效液相色谱法(HPLC)检测给药后各个时间点的血药浓度。结果显示:最低检测限为0.01μg/mL,线性范围为0.01～84.00μg/mL。诃子在异育银鲫体内的药动学过程符合一级吸收二室开放房室模型(1/C/C),其药物动力学方程为C=39.237e-0.320t+4.814e-0.006t,主要药动学参数为:吸收速率常数(Ka)为0.56 h-1,吸收半衰期(t1/2ka)为1.238 h,分布半衰期(t1/2α)为2.164 h,消除半衰期为(t1/2β)为119.369 h,达峰时间(Tmax)为4 h,最大血药浓度(Cmax)为11.024μg/mL,血药浓度-时间曲线下面积(AUC(0-∞))=674.89μg.h/mL,延滞时间(TL)为0.286 h,药物平均滞留时间(MRT(0-∞))=113.626 h,总体消除率(CLs)为0.112 L/(kg.h),表观分布容积(Vd)为13.713 L/kg。这些参数表明,异育银鲫口灌诃子后,能比较迅速被吸收,并且在血浆中维持较长的时间,具有较好的应用价值基础。

Pharmacokinetics of gallic acid of Fructus chebulae in Carassius auratus gibelio

Carassius auratus gibelio was administered orally with Fructus chebulae aqueous solution in a single dose of 77 mg/kg body weight at water temperature of(20±1)℃.The gallic acid concentration in C.auratus gibelio plasma were analyzed by high performance liquid chromatography(HPLC).The results were as follows:the lower limit of detection was 0.01 μg/mL,linear range was 0.01～84.00 μg/mL.The pharmacokinetic process of gallic acid of F.chebulae in C.auratus gibelio could be decribed by two-compartment open model with 1st order absorption(weight=1/C/C),and the pharmacokinetic model was C=39.237e-0.32t+4.814e-0.006t.The main pharmacokinetic parameters was as follows:absorption rate constant(Ka)=0.56 h-1,absorption half-life(t1/2ka)=1.238 h,distribution half-life(t1/2α)=2.164 h,elimination half-life(t1/2β)=119.369 h,the time to the peak drug concentration(Tmax)=4 h,the peak drug concentration(Cmax)=11.024 μg/mL,the area under the concentration-time curve from zero to infinity(AUC(0-∞))=674.89 μg·h/mL,the TL is 0.286 h,the MRT is 113.626 h,the CLs is 0.112 l/(kg·h),the Vd is 13.713 l/kg.The parameters indicated that the F.chebulae would be absorbed by C.auratus gibelio rapidly after single oral administration and maintained for a long time in plasma.Therefore,F.chebulae was of great value for the control of the fish disease.