Central Laboratory, Shanghai Xuhui Central Hospital, Shanghai, China.
Acta Pharmacol Sin. 2012 Oct;33(10):1332-6. doi: 10.1038/aps.2012.79. Epub 2012 Aug 20.
Dehydroandrographolide succinate (DAS) is extracted from herbal medicine Andrographis paniculata (Burm f) Nees. DAS injection is used in China for the treatment of viral pneumonia and upper respiratory tract infections. The aim of this study is to investigate the pharmacokinetics and tolerance of DAS injection in healthy Chinese volunteers.
This was a single-center, randomized, single-dose, three-way crossover design study. Nine eligible subjects were randomly divided into 3 groups, and each group sequentially received 80, 160, or 320 mg of DAS infusion according to a three-way Latin square design. Plasma and urine samples were collected and determined using an LC-MS/MS method. Safety and tolerability were determined via clinical evaluation and adverse event monitoring.
For the 80, 160, and 320 mg dose groups, the mean C(max) were 4.82, 12.85, and 26.90 mg/L, respectively, and the mean AUC(0-12) were 6.18, 16.95, and 40.65 mg·L(-1)·h, respectively. DAS was rapidly cleared, with a mean T(max) of 0.94-1.0 h and a t(1/2) of approximately 1.51-1.89 h. Approximately 10.1%-15.5% of the intravenous DAS dose was excreted unchanged in urine within 24 h in the 3 groups, and more than 90% of unchanged DAS was excreted between 0 and 4 h. The pharmacokinetic profile was similar between male and female subjects. No serious or unexpected adverse events were found during the study, but one mild adverse event (stomachache) was reported.
This study shows that DAS has nonlinear pharmacokinetic characteristics. To guarantee the effective concentration, mul¬tiple small doses are recommended in clinical regimens.
琥珀酸脱氢穿心莲内酯（DAS）是从草药穿心莲（Burm f）Nees 中提取的。在中国，DAS 注射液用于治疗病毒性肺炎和上呼吸道感染。本研究旨在研究 DAS 注射液在健康中国志愿者中的药代动力学和耐受性。
这是一项单中心、随机、单剂量、三向交叉设计研究。9 名合格受试者随机分为 3 组，每组按三向拉丁方设计顺序接受 80、160 或 320mg 的 DAS 输注。采用 LC-MS/MS 法测定血浆和尿液样本。通过临床评估和不良事件监测确定安全性和耐受性。
对于 80、160 和 320mg 剂量组，C（max）的平均值分别为 4.82、12.85 和 26.90mg/L，AUC（0-12）的平均值分别为 6.18、16.95 和 40.65mg·L（-1）·h。DAS 清除迅速，T（max）为 0.94-1.0h，t（1/2）约为 1.51-1.89h。3 组中，约 10.1%-15.5%的静脉内 DAS 剂量在 24 小时内以原形尿液排泄，90%以上的原形 DAS 在 0-4 小时内排泄。男女受试者的药代动力学特征相似。研究过程中未发现严重或意外的不良事件，但报告了 1 例轻度不良事件（胃痛）。
本研究表明 DAS 具有非线性药代动力学特征。为保证有效浓度，建议在临床方案中采用多次小剂量。
