Li Ping, Tian Yihua, Wang Hong, Ji Yuting, Zeng Huiying, Zhang Shengman, Gao Xiuli, Chen Xiaoyan
School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 561113, China.
Zhongshan Institute for Drug Discovery, Zhongshan 528437, China.
Pharmaceutics. 2025 Jun 29;17(7):851. doi: 10.3390/pharmaceutics17070851.
: Baicalin (BG) has been used in the treatment of many diseases. However, the effect of hepatic insufficiency on its pharmacokinetics has not been reported, and there is a lack of clinical guidance for the use of BG in patients with hepatic impairment. : Carbon tetrachloride (CCl)-induced rat models were used to simulate hepatic failure patients to assess the effect of hepatic impairment on the pharmacokinetics and distribution of BG. In vitro metabolism and transporter studies were employed to elucidate the potential mechanisms. : After intragastric administration of 10 mg/kg of BG, the peak plasma concentration and exposure (AUC) of BG decreased by 64.6% and 52.6%, respectively, in CCl-induced rats. After intravenous administration, the AUC decreased by 73.6%, and unlike in the control group, the second absorption peak of BG was not obvious in the concentration-time curve of CCl-induced rats. The cumulative excretion of BG in the feces increased, but that in the bile decreased. In vivo data indicated that the absorption and enterohepatic circulation of BG were affected. In vitro studies found that the hydrolysis of BG to the aglycone baicalein decreased significantly in the intestinal tissues and contents of the CCl-induced rats. And BG was identified as a substrate for multiple efflux and uptake transporters, such as breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins (MRPs), organic anion transporting polypeptides (OATP1B1, 1B3, 2B1), and organic anion transporters (OATs). The bile acids accumulated by liver injury inhibited the uptake of BG by OATPs, especially that by OATP2B1. : Hepatic impairment reduced BG hydrolysis by intestinal microflora and inhibited its transporter-mediated biliary excretion, which synergistically led to the attenuation of the enterohepatic circulation of BG, which altered its pharmacokinetics.
黄芩苷（BG）已被用于治疗多种疾病。然而，肝功能不全对其药代动力学的影响尚未见报道，且在肝损伤患者中使用BG缺乏临床指导。：采用四氯化碳（CCl）诱导的大鼠模型模拟肝衰竭患者，以评估肝损伤对BG药代动力学和分布的影响。采用体外代谢和转运体研究来阐明潜在机制。：给予10mg/kg BG灌胃后，CCl诱导的大鼠中BG的血浆峰浓度和暴露量（AUC）分别下降了64.6%和52.6%。静脉给药后，AUC下降了73.6%，与对照组不同，CCl诱导的大鼠浓度-时间曲线中BG的第二个吸收峰不明显。BG在粪便中的累积排泄增加，但在胆汁中的累积排泄减少。体内数据表明BG的吸收和肠肝循环受到影响。体外研究发现，在CCl诱导的大鼠肠组织和肠内容物中，BG水解为苷元黄芩素的过程显著减少。并且BG被鉴定为多种外排和摄取转运体的底物，如乳腺癌耐药蛋白（BCRP）和多药耐药相关蛋白（MRPs）、有机阴离子转运多肽（OATP1B1、1B3、2B1）以及有机阴离子转运体（OATs）。肝损伤积累的胆汁酸抑制了OATPs对BG的摄取，尤其是对OATP2B1的摄取。：肝损伤减少了肠道微生物群对BG的水解，并抑制了其转运体介导的胆汁排泄，这协同导致BG肠肝循环减弱，从而改变了其药代动力学。
