TY  - JOUR
PY  - 2017//
TI  - Describing the holistic toxicokinetics of hepatotoxic Chinese herbal medicines by a novel integrated strategy: Dioscorea bulbifera rhizome as a case study
JO  - Journal of chromatography B: analytical technologies in the biomedical and life sciences
A1  - Wang, Ling-Li
A1  - Zhao, Dong-Sheng
A1  - Shi, Wei
A1  - Li, Zhuo-Qing
A1  - Wu, Zi-Tian
A1  - Li, Ping
A1  - Li, Hui-Jun
SP  - 40
EP  - 48
VL  - 1064
IS  - 
N2  - It is vital to monitor the holistic toxicokinetics of toxic Chinese herbal medicines (CHMs) for safety. Although an integrated strategy based on the area under the curve (AUC) has been proposed to characterize the pharmacokinetic/toxicokinetic properties of CHMs, improvement is still needed. This study attempted to use 50% inhibitory concentration (IC50) as weighting coefficient to investigate holistic toxicokinetics of the major diosbulbins i.e. diosbulbin A (DA), diosbulbin B (DB), and diosbulbin C (DC) after oral administration of Dioscorea bulbifera rhizome (DBR) extract. Firstly, the cytotoxicities of the three diosbulbins on human hepatic L02 cells were evaluated and the IC50 values were calculated. Then, integrated toxicokinetics of multiple diosbulbins based on AUC and IC50 were determined. Finally, correlations between integrated plasma concentrations and hepatic injury biomarkers including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bile acid (TBA) were analyzed. As a result, integrated plasma concentrations were correlated well with TBA and the correlation between TBA and IC50-weighting integrated plasma concentrations was better than that of AUC-weighting integrated plasma concentrations. In conclusion, the newly developed IC50-weighting method is expected to generate more reasonable integrated toxicokinetic parameters, which will help to guide the safe usage of DBR in clinical settings.<br><br>Copyright © 2017 Elsevier B.V. All rights reserved.<p />  <p>Language: en</p>
LA  - en
SN  - 1570-0232
UR  - http://dx.doi.org/10.1016/j.jchromb.2017.08.040
ID  - ref1
ER  -