黄连、吴茱萸药对中盐酸小檗碱在急性胃溃疡模型大鼠体内的药代动力学研究

Pharmacokinetics studied on berberine hydrochloride acted by rhizoma coptidis-fructus evodiae herbal couple in acute gastric ulcer rats

目的比较黄连-吴茱萸药对提取液中盐酸小檗碱在急性胃溃疡模型大鼠与正常大鼠体内的药代动力学差异,探讨病理状态对盐酸小檗碱体内过程的影响。方法分别灌胃给予正常大鼠和急性胃溃疡模型大鼠黄连-吴茱萸(6:1)药对提取液,采用高效液相色谱方法测定大鼠体内盐酸小檗碱的血浆浓度,色谱柱:Diamonsil C18(150mm×4.6mm,5μm);流动相:乙腈-甲醇-0.05mol/L磷酸二氢钾溶液(23∶12∶65),流速:1.0ml/min;检测波长:345nm;柱温:30℃。结果盐酸小檗碱在正常组的药代动力学参数:Cmax=0.064±0.01μg/ml;Tmax=(0.42±0.13)h;t1/2=(5.96±1.16)h;AUC0-t=(0.42±0.08)μg/(ml.h);AUC0-∞=(0.45±0.09)μg/(ml.h)。盐酸小檗碱在模型组的药代动力学参数:Cmax=(0.069±0.01)μg/ml;Tmax=(0.54±0.11)h;t1/2=(5.11±1.78)h;AUC0-t=(0.60±0.17)μg/(ml.h);AUC0-∞=(0.63±0.18)μg/(ml.h)。结论黄连-吴茱萸药对在乙醇致急性胃溃疡模型大鼠中吸收减慢,但是吸收量多,体内滞留时间稍延长。

Objective To explore the pathological effect on berberine hydrochloride based on the pharmacokinetic research of berberine hydrochloride acted by rhizoma coptis-fructus evodia herbal couple in normal rats and acute gastric ulcer rats respectively.Methods Rats in each group were orally administered with rhizoma coptis-fructus evodia herbal couple（6：1）,and then the in vivo plasma concentrations of berberine hydrochloride were determined by high performance liquid chromatographic（HPLC） method.Chromatogram column： Diamonsil C18（150mm×4.6mm,5μm）;the mobile phase： Acetonitrile-methanol-0.05mol/L potassium dihydrogen phosphate solution（23：12：65）;the flow rate： 1.0ml/min;the UV detector was operated at 345 nm and the column temperature was controlled at 30℃.Results The main pharmacokinetic parameters of berberine hydrochloride in the two groups were as follow.Pharmacokinetics parameters of the normal group of berberine hydrochloride： Cmax=（0.064±0.01）μg/ml;Tmax=（0.42±0.13）h;t1/2=（5.96±1.16）h;AUC0-t=（0.42±0.08）μg/（ml·h）;AUC0-∞=（0.45± 0.09）μg/（ml·h）;Pharmacokinetics parameters of the acute gastric ulcer group of berberine hydrochloride： Cmax=（0.069±0.01）μg/ml;Tmax=（0.54±0.11）h;t1/2=（5.11±1.78）h;AUC0-t=（0.60±0.17）μg/（ml·h）;AUC0-∞=（0.63±0.18）μg/（ml·h）.Conclusion Rhizoma coptis-Fructus evodia herbal couple can slow the absorption but increase the dose and retention time in plasma of berberine hydrochloride in the acute gastric ulcer rats caused by alcohol.