Sadakane Chiharu, Watanabe Junko, Fukutake Miwako, Nisimura Hiroaki, Maemura Kazuya, Kase Yoshio, Kono Toru
Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki, Japan.
Tsumura Research Laboratories, Kampo Scientific Strategies Division, Tsumura & Co., Ibaraki, Japan.
J Pharm Sci. 2015 Nov;104(11):3952-3959. doi: 10.1002/jps.24596. Epub 2015 Jul 24.
Shakuyakukanzoto (SKT), a traditional Japanese (Kampo) medicine, has been used by patients with muscle cramps and abdominal pains. In this trial, we analyzed plasma concentrations of active components after SKT was administered as a single oral dose of 2.5 or 5.0 g/day per person. The study was a randomized, open-label, two-arm, two-period, crossover trial conducted in healthy Japanese volunteers. Albiflorin (ALB), paeoniflorin (PAE), glycycoumarin (GCM), isoliquiritigenin (ILG), glycyrrhetic acid (GA), and glycyrrhetic acid-3-O-monoglucuronide were targeted, and the plasma concentration of each component was measured using a liquid chromatography-tandem mass spectrometry method. The pharmacokinetic parameters were calculated, and the linearity was assessed. All targeted components were detected in the plasma after oral administration of SKT. ALB, PAE, GCM, and ILG were detected at an early stage. The linearity was observed for the maximum plasma concentration of GCM, ILG, and GA and for the area under the plasma concentration-time curve of GA. In this trial, we demonstrated for the first time in humans that these components were absorbed into the blood after oral administration of SKT. The results of this pharmacokinetic trial in humans are also important and useful for understanding the mechanism of action of SKT, verifying the active components predicted in basic research, and conducting pharmacokinetics and safety studies in the future.
芍药甘草汤(SKT)是一种传统的日本(汉方)药物,已被用于治疗肌肉痉挛和腹痛患者。在本试验中,我们分析了每人每天单次口服2.5克或5.0克SKT后活性成分的血浆浓度。该研究是一项在健康日本志愿者中进行的随机、开放标签、双臂、两期交叉试验。以芍药苷(ALB)、芍药内酯苷(PAE)、甘草香豆素(GCM)、异甘草素(ILG)、甘草次酸(GA)和甘草次酸-3-O-单葡萄糖醛酸为研究对象,采用液相色谱-串联质谱法测定各成分的血浆浓度。计算药代动力学参数并评估线性关系。口服SKT后在血浆中检测到所有目标成分。ALB、PAE、GCM和ILG在早期被检测到。观察到GCM、ILG和GA的最大血浆浓度以及GA的血浆浓度-时间曲线下面积呈线性关系。在本试验中,我们首次在人体中证明这些成分在口服SKT后被吸收进入血液。该人体药代动力学试验的结果对于理解SKT的作用机制、验证基础研究中预测的活性成分以及未来进行药代动力学和安全性研究也具有重要意义和实用价值。