功劳去火片中黄芩苷和小檗碱在大鼠体内的药物动力学

Parmacokinetics of bacalin and berberine Gonglao Quhuo tablets in rats

目的建立同时测定大鼠体内黄芩苷和小檗碱血药浓度的方法,用于研究功劳去火片中两种指标成分的药物动力学。方法给予大鼠ig功劳去火片制得混悬液,给药前及给药后不同时间采集血样,采用HPLC法测定血样中的黄芩苷和小檗碱,药-时数据经3p97软件分析处理,并与文献比较,判断给药形式的影响。结果黄芩苷和小檗碱的线性范围分别为0.061～3.910、0.017～1.060μg.ml-1,最低定量限分别为0.061、0.017μg.ml-1。两者的平均回收率均大于97.2%,精密度与准确度均符合生物样品分析要求。给药后,黄芩苷在大鼠体内的代谢符合二室模型,主要药动学参数为:K21=0.74±0.301/h,K10=0.143±0.0351/h,K12=1.26±0.801/h,t1/2β=13.5±1.0h,t1/2α=0.40±0.18h,Tmax=0.352±0.086h,Cmax=0.94±0.18μg.ml-1。小檗碱符合一室模型,其主要药动学参数为:t1/2(Ke)=3.65±0.96h,t1/2(Ka)=0.073±0.019h,t1/2(Km)=0.076±0.022h,Tmax=0.60±0.12h,Cmax=0.254±059μg.ml-1。结论功劳去火片中黄芩苷和小檗碱的药物动力学受中药复方给药形式的影响,与单指标成份给药有差异。

OBJECTIVE To establish a method for simultaneous determination of baicalin and berberine in plasma, which as major index components in Gonglao Quhuo tablets, study of baicalin and berberine in rats in vivo to discuss the effect on pharmacokinet- ic. METHODS After intragastic administration of Gonglao Quhuo tablets, the plasma was collected at different times from untreated to treated groups for 24 h,and then baicalin and berberine concentration in rat plasma were determined. The data were calculated with 3p97 software,and then compared with pertinent literature. RESULTS The liner range of baicalin and berberine were 0. 061 - 3.91 μg·ml-1 （r =0. 9997） and 0. 017 - 1.06μg·ml-1 （r =0. 9999）, respectively. The lower limit of quantitation （LLOQ） of baicalin and berberine were 0. 061 μg·ml-1 and 0. 017 μg·ml-1, with accuracy and precision conformed to the requirement of biological specimen analysis. The distribution of bacailin and berberine in rats were conformed to be a two - compartment model and one - compartment model, respectively. The important pharmacokinetic parameters of baicalin ：K21 was 0. 740 ± 0. 30 1/h,Kl0 was 0. 143 ± 0. 035 1/h,K12 was 1.26 ±0. 8 1/h,t1/2g and tl/2β were 13.5 ± 1.0 h and 0.40 ＋0.18 h,Tmax was 0. 352 ±0. 086 h,Cmax, was 0. 940 ±0. 18 μg·ml-1, respectively. The important pharmacokinetic parameters of berberine ：t1/2（Kc） was 3.65 ± 0. 69 h, t1/2（Ka） was 0. 073 ± 0. 019 b, t1/2（Km） was 0. 076 ± 0. 022 h, Tmax was 0. 605 ± 0. 12 h, Cmax was 0. 254 ± 059 μg·ml-1, respectively. CONCLUSION The established method was simple and suitable for determination of plasma concentration of baicalin and berberine. Their pharmacokinetics were influ- ened by the medication form and the components of the TCM.