Songvut Phanit, Akanimanee Jaratluck, Suriyo Tawit, Pholphana Nanthanit, Rangkadilok Nuchanart, Panomvana Duangchit, Puranajoti Porranee, Satayavivad Jutamaad
Laboratory of Pharmacology, Chulabhorn Research Institute, Bangkok, Thailand.
Center of Excellence on Environmental Health and Toxicology (EHT), OPS, MHESI, Bangkok, Thailand.
Pharm Biol. 2025 Dec;63(1):42-52. doi: 10.1080/13880209.2024.2444446. Epub 2025 Jan 6.
Insufficient quality control and limited dissolution of extract capsules restricts their bioavailability and hinder the clinical use for treating mild coronavirus disease 2019 (COVID-19) patients.
This study aims to investigate pharmacokinetics and safety of high-dosage ethanolic extract (equivalent to 180 or 360 mg/day of andrographolide), relevant dosages used for mild COVID-19 treatment.
An open-label, single-dose, and repeated-dose conducted in healthy volunteers. Subjects received capsules containing ethanolic extract equivalent to andrographolide dosage of either 60 or 120 mg per dose, taken every eight hours daily (totaling 180 or 360 mg/day). Safety was assessed through blood chemical analysis and adverse event monitoring after 7 days of ethanolic extract administration.
Pharmacokinetics of ethanolic extract indicated low plasma levels of the major diterpenoids. The maximum plasma concentration (Cmax) of andrographolide did not exhibit a dose-proportional increase, reaching 6.44 and 11.62 µg/L for single and repeated doses of 60 mg/day, respectively. Doubling the dose (120 mg/day) only resulted in slightly higher Cmax (6.97 and 15.03 µg/L for single and repeated doses, respectively). Safety evaluation revealed mild, transient adverse events, but all parameters remained within normal ranges.
This study highlights limitations in the pharmacokinetics of the ethanolic extract of . It indicated non-linear proportionality in the oral bioavailability of andrographolide. These findings suggest that current extraction process of ethanolic extract may hinder its effectiveness. Further research is warranted to explore alternative extraction methods or formulation developments that can enhance the bioavailability of andrographolide and its potential therapeutic effects for COVID-19 treatment.
提取物胶囊质量控制不足和溶出受限限制了其生物利用度，并阻碍了其在治疗新型冠状病毒肺炎（COVID-19）轻症患者中的临床应用。
本研究旨在调查高剂量乙醇提取物（相当于穿心莲内酯180或360mg/天，这是用于COVID-19轻症治疗的相关剂量）的药代动力学和安全性。
在健康志愿者中进行开放标签、单剂量和重复剂量研究。受试者接受每剂量含相当于穿心莲内酯60或120mg的乙醇提取物胶囊，每天每8小时服用一次（总计180或360mg/天）。在给予乙醇提取物7天后，通过血液化学分析和不良事件监测评估安全性。
乙醇提取物的药代动力学表明主要二萜类化合物的血浆水平较低。穿心莲内酯的最大血浆浓度（Cmax）未呈现剂量比例增加，60mg/天单剂量和重复剂量时分别达到6.44和11.62μg/L。剂量加倍（120mg/天）仅导致Cmax略高（单剂量和重复剂量时分别为6.97和15.03μg/L）。安全性评估显示有轻度、短暂的不良事件，但所有参数均保持在正常范围内。
本研究突出了乙醇提取物药代动力学的局限性。它表明穿心莲内酯的口服生物利用度存在非线性比例关系。这些发现表明目前乙醇提取物的提取工艺可能会阻碍其有效性。有必要进一步研究探索可提高穿心莲内酯生物利用度及其对COVID-19治疗潜在疗效的替代提取方法或制剂开发。
