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.

监测有毒中草药（CHMs）的整体毒物代谢动力学的安全性至关重要。尽管已提出了基于曲线下面积（AUC）的集成策略来表征CHM的药代动力学/毒代动力学特性，但仍需要改进。这项研究尝试使用50％抑制浓度（IC ₅₀）作为加权系数，以研究口服薯os根茎后主要薯os的整体毒物动力学，即薯bul A（DA），薯os B（DB）和薯bul C（DC）。（DBR）提取物。首先，评估了三种薯os对人肝L02细胞的细胞毒性，并测定了IC ₅₀计算值。然后，基于AUC和IC ₅₀确定了多个薯bul的综合毒物动力学。最后，分析了综合血浆浓度与肝损伤生物标志物之间的相关性，包括丙氨酸转氨酶（ALT），天冬氨酸转氨酶（AST），碱性磷酸酶（ALP）和总胆汁酸（TBA）。结果，积分血浆浓度与TBA很好地相关，并且TBA和IC ₅₀加权积分血浆浓度之间的相关性优于AUC加权积分血浆浓度。总之，新开发的IC ₅₀加权法有望产生更合理的综合毒物动力学参数，这将有助于指导DBR在临床环境中的安全使用。