Exploratory pharmacokinetic-pharmacodynamic characterization and safety of standardized Andrographis paniculata aqueous extract capsules in patients with mild COVID-19

Phanit Songvut¹Paruspak Payoong²Pilailuk Akkapaiboon Okada³Noppawan Rittapai¹Sumitra Suntararuks¹Jaratluck Akanimanee¹Nuchanart Rangkadilok¹Duangchit Panomvana⁴Porranee Puranajoti⁴Jutamaad Satayavivad^1*

• ¹Chulabhorn Research Institute Laboratory of Pharmacology, Bangkok, Thailand
• ²Chulabhorn Royal Academy, Bangkok, Thailand
• ³Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand
• ⁴Translational Research Unit, Chulabhorn Research Institute, Bangkok, Thailand

Introduction: Andrographis paniculata has been used in the management of COVID-19-related conditions during the SARS-CoV-2 pandemic. However, human pharmacokinetic-pharmacodynamic (PK/PD) evidence to support a rationale for safe and evidence-based dosing of standardized extracts in clinical use remains limited. This exploratory study aimed to investigate the pharmacokinetics, preliminary PK/PD relationship, and short-term safety profile of standardized A. paniculata aqueous extract capsules in patients with mild COVID-19. Methods: A single-center PK/PD clinical trial with two sequential phases (single-dose follow by multiple-dose) was conducted. Patients with mild COVID-19 received standardized A. paniculata aqueous extract capsules equivalent to 30 mg of andrographolide every 8 hours (90 mg/day) for 5 consecutive days, alongside standard symptomatic treatment. Results: Rapid absorption and elimination with limited systemic exposure supported repeated dosing to maintain exposure over the 5-day period. PK/PD analysis demonstrated a sigmoidal, saturable exposure-response relationship. The mean area under the concentration–time curve (AUC0-4 h) on day 5 approached the estimated EAUC50 (half-maximal effective exposure) derived from the Emax model. A -2.96 log10 reduction in viral load was observed; however, without a placebo control group, it is not possible to conclusively attribute this reduction to the investigational A. paniculata aqueous extract capsules. Adverse events were mild, with no hepatotoxicity or renal toxicity observed. Conclusion: These findings provide preliminary evidence regarding the pharmacokinetics, dose-exposure characteristics, and short-term tolerability of standardized A. paniculata aqueous extract capsules, supporting further investigation in patients with mild COVID-19. Larger, placebo-controlled trials are warranted to establish causality and to evaluate clinical benefits.