Ye Linhu, Cheng Lei, Deng Yan, Wang Sen, Wu Xinyu, Ou Shuiping, Chang Qi, Zhao Xinqian, Zhou Wen, Yu Jinghua, Wu Zuqiang
The Sixth Affiliated Hospital, School of Medicine, South China University of Technology, Nanhai District People's Hospital of Foshan, Foshan, China.
Bijie City First People's Hospital, Bijie, China.
Front Pharmacol. 2023 Jul 7;14:1216985. doi: 10.3389/fphar.2023.1216985. eCollection 2023.
Licorice ( Fisch) is a natural plant resource widely used as a food and herbal medication in China. Glycycoumarin (GCM) is a major coumarin in licorice that possesses several biological activities. However, little is known about its pharmacokinetic profile. The present study aimed to describe the oral absorption, tissue distribution, and excretion of GCM in rats. Free (parent drug) and/or total (parent drug plus the glucuronidated metabolite) GCM in biological samples was quantified before and after the hydrolysis reaction with -glucuronidase using a reliable LC-MS/MS method. The results indicated that GCM was rapidly absorbed and transformed into its conjugated metabolites after administration. Free GCM plasma concentrations after (10 mg/kg) administration quickly decreased with an average t of 0.71 h, whereas the total GCM concentration reduced slowly with a t of 2.46 h. The area under the curve of glucuronidated metabolites was approximately four-times higher than that of free GCM. Presumably, because of hepatic and/or intestinal tract first-pass metabolism, GCM exhibited a poor bioavailability of 9.22%, as estimated from its total plasma concentration. Additionally, GCM was distributed rapidly and widely in various tissues except the brain. The liver had the highest concentration; further, GCM was promptly eliminated from test tissues after intraperitoneal (20 mg/kg) administration, but only a small amount of GCM was excreted via bile and urine. Overall, GCM is absorbed and rapidly transformed into its conjugated metabolites with low bioavailability; further, it is distributed in various tissues, except the brain. These pharmacokinetic results are helpful for better understanding the characteristics and pharmacological effects of GCM.
甘草（甘草属）是一种在中国被广泛用作食品和草药的天然植物资源。甘草香豆素（GCM）是甘草中的一种主要香豆素，具有多种生物活性。然而，对其药代动力学特征知之甚少。本研究旨在描述GCM在大鼠体内的口服吸收、组织分布和排泄情况。使用可靠的液相色谱-串联质谱法（LC-MS/MS）对生物样品中游离（母体药物）和/或总（母体药物加葡萄糖醛酸化代谢物）GCM在与β-葡萄糖醛酸酶水解反应前后进行定量。结果表明，GCM给药后迅速吸收并转化为其结合代谢物。给予10mg/kg剂量后，游离GCM血浆浓度迅速下降，平均半衰期为0.71小时，而总GCM浓度下降缓慢，半衰期为2.46小时。葡萄糖醛酸化代谢物的曲线下面积约为游离GCM的四倍。据推测，由于肝脏和/或肠道首过代谢，根据其总血浆浓度估计，GCM的生物利用度较差，为9.22%。此外，GCM在除脑以外的各种组织中迅速且广泛地分布。肝脏中的浓度最高；此外，腹腔注射20mg/kg剂量后，GCM在受试组织中迅速消除，但只有少量GCM通过胆汁和尿液排泄。总体而言，GCM被吸收并迅速转化为其结合代谢物，生物利用度低；此外，它分布于除脑以外的各种组织中。这些药代动力学结果有助于更好地理解GCM的特性和药理作用。
