目的 研究黄独素B(DIOB)在大鼠体内的血浆药动学和组织分布特征,并比较DIOB单体和黄药子醇提物(EEDB)给药后DIOB血浆和组织暴露以及消除的差异.方法 建立并验证了定量分析血浆和组织样品DIOB的液相-串联质谱法(LC-MS/MS).SD大鼠ig给予DIOB 1.3 mg·kg-1和EEDB 1.0 g·kg-1,不同时间点采样,测定血浆和组织样品中的DIOB浓度.快速平衡透析法测定DIOB在血浆和组织的蛋白结合率.采用WinNonlin 6.4软件拟合并获得药动学参数.结果 大鼠给予DIOB单体和EEDB后,血浆DIOB的峰浓度(cmax)和达峰时间(tmax)分别为312±67和(131±84)μg·L-1(P48.结论 DIOB以单体和EEDB 2种形式给药后,大鼠血浆动力学和组织分布存在一定的差异.DIOB在肺组织的分布具有较强的靶向性.在黄药子和DIOB的药效学和毒理学研究中应关注上述特征和差异.%OBJECTIVE To characterize pharmacokinetics and tissue distribution of diosbulbin B (DIOB)in rats,and compare exposure and elimination of DIOB in plasma and tissues after ig adminis-tration of compound DIOB and ethanol extract of Dioscorea bulbifera L.(EEDB),respectively.METHODS Liquid chromatography coupled with tandem mass spectrometry method was developed and validated for quantitative determination of DIOB in plasma and tissue samples. The sensitivity, matrix effect, accuracy and precision of the method were determined. After a single ig administration of DIOB 1.3 mg·kg-1and EEDB 1.0 g·kg-1, respectively, plasma and tissues samples were collected separately from male SD rats at prescheduled time points.The drug-protein binding of DIOB in plasma and tissues was measured using Rapid Equilibrium Dialysis Assay. The concentration-time profiles of DIOB were analyzed using WinNonLin 6.4 to obtain pharmacokinetic parameters. RESULTS Rapid absorption and elimination of DIOB were observed in rats.The plasma maximum concentration(cmax),peak time(tmax) and eliminate half life(t1/2)of DIOB in rats receiving DIOB or EEDB were 312±67 and(131±84)μg·L-1(P<0.01), 0.12 ± 0.07 and (0.23 ± 0.17) h, and 1.17 ± 0.28 and (2.34 ± 0.83) h (P<0.05). DIOB was rapidly distributed in most tissues,with the AUC(0-24 h)of DIOB in lungs,liver and kidneys for DIOB and EEDB groups were 4527.0±557.7,183.0±51.1 and(64.4±22.4)ng·h·g-1,and 6507.9±424.3(P<0.01),467.5±202.7(P<0.05) and (238.6 ± 70.0) ng·h·g-1(P<0.05), respectively. The protein binding rate of DIOB was 38.7%-43.6%,61.3%-66.9% and 61.4%-64.7% in plasma,livers and lungs,respectively.The ratio of free concen-trations between tissue and plasma for lungs was more than 48,indicating the specific distribution of DIOB in lungs.CONCLUSION There is difference in pharmacokinetics and tissue distribution of DIOB in rats after taking compound DIOB and EEDB.Among the tissues detected,lungs are the major target of DIOB with the highest exposure level.These characterizations should be considered in pharmacological and toxicological studies of DIOB and relevant herbs.
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