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

DOI record: { "DOI": "10.3389/fphar.2026.1781740", "ISSN": [ "1663-9812" ], "URL": "http://dx.doi.org/10.3389/fphar.2026.1781740", "abstract": "<jats:sec>\n <jats:title>Introduction</jats:title>\n <jats:p>\n <jats:italic>Andrographis paniculata</jats:italic>\n 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\n <jats:italic>A. paniculata</jats:italic>\n aqueous extract capsules in patients with mild COVID-19.\n </jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>\n A single-center PK/PD clinical trial with two sequential phases (single-dose followed by multiple-dose) was conducted. Patients with mild COVID-19 received standardized\n <jats:italic>A. paniculata</jats:italic>\n aqueous extract capsules equivalent to 30 mg of andrographolide every 8 h (90 mg/day) for 5 consecutive days, alongside standard symptomatic treatment.\n </jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>\n 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 (AUC\n <jats:sub>0-4 h</jats:sub>\n ) on day 5 approached the estimated EAUC\n <jats:sub>50</jats:sub>\n (half-maximal effective exposure) derived from the Emax model. A −2.96 log\n <jats:sub>10</jats:sub>\n reduction in viral load was observed; however, without a placebo control group, it is not possible to conclusively attribute this reduction to the investigational\n <jats:italic>A. paniculata</jats:italic>\n aqueous extract capsules. Adverse events were mild, with no hepatotoxicity or renal toxicity observed.\n </jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Conclusion</jats:title>\n <jats:p>\n These findings provide preliminary evidence regarding the pharmacokinetics, dose-exposure characteristics, and short-term tolerability of standardized\n <jats:italic>A. paniculata</jats:italic>\n 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.\n </jats:p>\n </jats:sec>", "alternative-id": [ "10.3389/fphar.2026.1781740" ], "article-number": "1781740", "author": [ { "affiliation": [ { "name": "Laboratory of Pharmacology, Chulabhorn Research Institute", "place": [ "Bangkok, Thailand" ] }, { "name": "Center of Excellence on Environmental Health and Toxicology (EHT), OPS, MHESI", "place": [ "Bangkok, Thailand" ] } ], "family": "Songvut", "given": "Phanit", "sequence": "first" }, { "affiliation": [ { "name": "Department of Medicine, Chulabhorn Hospital, Chulabhorn Royal Academy", "place": [ "Bangkok, Thailand" ] } ], "family": "Payoong", "given": "Paruspak", "sequence": "additional" }, { "affiliation": [ { "name": "National Institute of Health, Department of Medical Sciences, Ministry of Public Health", "place": [ "Nonthaburi, Thailand" ] } ], "family": "Okada", "given": "Pilailuk Akkapaiboon", "sequence": "additional" }, { "affiliation": [ { "name": "Laboratory of Pharmacology, Chulabhorn Research Institute", "place": [ "Bangkok, Thailand" ] } ], "family": "Rittapai", "given": "Noppawan", "sequence": "additional" }, { "affiliation": [ { "name": "Laboratory of Pharmacology, Chulabhorn Research Institute", "place": [ "Bangkok, Thailand" ] } ], "family": "Suntararuks", "given": "Sumitra", "sequence": "additional" }, { "affiliation": [ { "name": "Laboratory of Pharmacology, Chulabhorn Research Institute", "place": [ "Bangkok, Thailand" ] } ], "family": "Akanimanee", "given": "Jaratluck", "sequence": "additional" }, { "affiliation": [ { "name": "Laboratory of Pharmacology, Chulabhorn Research Institute", "place": [ "Bangkok, Thailand" ] }, { "name": "Center of Excellence on Environmental Health and Toxicology (EHT), OPS, MHESI", "place": [ "Bangkok, Thailand" ] } ], "family": "Rangkadilok", "given": "Nuchanart", "sequence": "additional" }, { "affiliation": [ { "name": "Translational Research Unit, Chulabhorn Research Institute", "place": [ "Bangkok, Thailand" ] } ], "family": "Panomvana", "given": "Duangchit", "sequence": "additional" }, { "affiliation": [ { "name": "Translational Research Unit, Chulabhorn Research Institute", "place": [ "Bangkok, Thailand" ] } ], "family": "Puranajoti", "given": "Porranee", "sequence": "additional" }, { "affiliation": [ { "name": "Laboratory of Pharmacology, Chulabhorn Research Institute", "place": [ "Bangkok, Thailand" ] }, { "name": "Center of Excellence on Environmental Health and Toxicology (EHT), OPS, MHESI", "place": [ "Bangkok, Thailand" ] } ], "family": "Satayavivad", "given": "Jutamaad", "sequence": "additional" } ], "container-title": "Frontiers in Pharmacology", "container-title-short": "Front. Pharmacol.", "content-domain": { "crossmark-restriction": true, "domain": [ "frontiersin.org" ] }, "created": { "date-parts": [ [ 2026, 3, 13 ] ], "date-time": "2026-03-13T10:40:21Z", "timestamp": 1773398421000 }, "deposited": { "date-parts": [ [ 2026, 3, 13 ] ], "date-time": "2026-03-13T10:40:24Z", "timestamp": 1773398424000 }, "funder": [ { "DOI": "10.13039/501100004704", "doi-asserted-by": "publisher", "id": [ { "asserted-by": "publisher", "id": "10.13039/501100004704", "id-type": "DOI" } ], "name": "National Research Council of Thailand" }, { "DOI": "10.13039/501100007959", "doi-asserted-by": "publisher", "id": [ { "asserted-by": "publisher", "id": "10.13039/501100007959", "id-type": "DOI" } ], "name": "Chulabhorn Research Institute" } ], "indexed": { "date-parts": [ [ 2026, 3, 13 ] ], "date-time": "2026-03-13T14:51:40Z", "timestamp": 1773413500264, "version": "3.50.1" }, "is-referenced-by-count": 0, "issued": { "date-parts": [ [ 2026, 3, 13 ] ] }, "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2026, 3, 13 ] ], "date-time": "2026-03-13T00:00:00Z", "timestamp": 1773360000000 } } ], "link": [ { "URL": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1781740/full", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "1965", "original-title": [], "prefix": "10.3389", "published": { "date-parts": [ [ 2026, 3, 13 ] ] }, "published-online": { "date-parts": [ [ 2026, 3, 13 ] ] }, "publisher": "Frontiers Media SA", "reference": [ { "DOI": "10.26502/aimr.0146", "article-title": "Effect of Andrographis paniculata treatment for nonimmune patients with early-stage COVID-19 on the prevention of pneumonia: a retrospective cohort study", "author": "Benjaponpitak", "doi-asserted-by": "publisher", "first-page": "35", "journal-title": "Arch. Intern. Med. Res.", "key": "B1", "volume": "6", "year": "2023" }, { "DOI": "10.3109/13880209.2013.836544", "article-title": "Pharmacokinetic analysis and tissue distribution of andrographolide in rat by a validated LC–MS/MS method", "author": "Bera", "doi-asserted-by": "publisher", "first-page": "321", "journal-title": "Pharm. Biol.", "key": "B2", "volume": "52", "year": "2014" }, { "DOI": "10.1111/cts.70184", "article-title": "Comparison of molnupiravir exposure‐response relationships for virology response and mechanism of action biomarkers with clinical outcomes in treatment of COVID‐19", "author": "Chawla", "doi-asserted-by": "publisher", "first-page": "e70184", "journal-title": "Clin. Transl. Sci.", "key": "B3", "volume": "18", "year": "2025" }, { "DOI": "10.3389/fphar.2022.950012", "article-title": "Therapeutic effects of herbal-medicine combined therapy for COVID-19: a systematic review and meta-analysis of randomized controlled trials", "author": "Chien", "doi-asserted-by": "publisher", "first-page": "950012", "journal-title": "Front. Pharmacol.", "key": "B4", "volume": "13", "year": "2022" }, { "DOI": "10.1080/10408398.2018.1501657", "article-title": "Overview of pharmacological activities of Andrographis paniculata and its major compound andrographolide", "author": "Dai", "doi-asserted-by": "publisher", "first-page": "S17", "journal-title": "Crit. Rev. Food Sci. Nutr.", "key": "B5", "volume": "59", "year": "2019" }, { "key": "B6", "volume-title": "Thai herbal pharmacopoeia", "year": "2021" }, { "DOI": "10.1078/094471102321616391", "article-title": "A double blind, placebo-controlled study of Andrographis paniculata fixed combination Kan Jang in the treatment of acute upper respiratory tract infections including sinusitis", "author": "Gabrielian", "doi-asserted-by": "publisher", "first-page": "589", "journal-title": "Phytomedicine", "key": "B7", "volume": "9", "year": "2002" }, { "DOI": "10.1371/journal.ppat.1010802", "article-title": "Infectious viral shedding of SARS-CoV-2 Delta following vaccination: a longitudinal cohort study", "author": "Garcia-Knight", "doi-asserted-by": "publisher", "first-page": "e1010802", "journal-title": "PLoS Pathog.", "key": "B8", "volume": "18", "year": "2022" }, { "DOI": "10.3390/molecules27144479", "article-title": "A comprehensive review of Andrographis paniculata (Burm. f.) Nees and its constituents as potential lead compounds for COVID-19 drug discovery", "author": "Intharuksa", "doi-asserted-by": "publisher", "first-page": "4479", "journal-title": "Molecules", "key": "B9", "volume": "27", "year": "2022" }, { "DOI": "10.1016/j.jtcme.2022.02.001", "article-title": "Natural products as a source of novel drugs for treating SARS-CoV2 infection", "author": "Isidoro", "doi-asserted-by": "publisher", "first-page": "1", "journal-title": "J. Tradit. Complement. Med.", "key": "B10", "volume": "12", "year": "2022" }, { "DOI": "10.1038/s41598-025-13652-6", "article-title": "Degradation kinetics of andrographolide in aqueous solution, product identification and biological activity evaluation", "author": "Jaidee", "doi-asserted-by": "publisher", "first-page": "28856", "journal-title": "Sci. Rep.", "key": "B11", "volume": "15", "year": "2025" }, { "DOI": "10.1039/d0ra10529e", "article-title": "Combination of system biology to probe the anti-viral activity of andrographolide and its derivative against COVID-19", "author": "Khanal", "doi-asserted-by": "publisher", "first-page": "5065", "journal-title": "RSC Adv.", "key": "B12", "volume": "11", "year": "2021" }, { "DOI": "10.1016/j.jtcme.2024.05.004", "article-title": "In vivo evaluation of Andrographis paniculata and Boesenbergia rotunda extract activity against SARS-CoV-2 Delta variant in golden Syrian hamsters", "author": "Kongsomros", "doi-asserted-by": "publisher", "first-page": "598", "journal-title": "J. Tradit. Complement. Med.", "key": "B13", "volume": "14", "year": "2024" }, { "DOI": "10.1007/s10096-020-03913-9", "article-title": "Viral RNA load as determined by cell culture as a management tool for discharge of SARS-CoV-2 patients from infectious disease wards", "author": "La Scola", "doi-asserted-by": "publisher", "first-page": "1059", "journal-title": "Eur. J. Clin. Microbiol. Infect. Dis.", "key": "B14", "volume": "39", "year": "2020" }, { "DOI": "10.1111/j.1440-1681.2011.05633.x", "article-title": "Andrographolide and its analogues: versatile bioactive molecules for combating inflammation and cancer", "author": "Lim", "doi-asserted-by": "publisher", "first-page": "300", "journal-title": "Clin. Exp. Pharmacol. Physiol.", "key": "B15", "volume": "39", "year": "2012" }, { "DOI": "10.3389/fimmu.2022.1062067", "article-title": "Robust humoral and cellular recall responses to AZD1222 attenuate breakthrough SARS-CoV-2 infection compared to unvaccinated", "author": "Maaske", "doi-asserted-by": "publisher", "first-page": "1062067", "journal-title": "Front. Immunol.", "key": "B16", "volume": "13", "year": "2023" }, { "DOI": "10.1002/jmv.27307", "article-title": "High proportion of low cycle threshold value as an early indicator of COVID‐19 surge", "author": "Mishra", "doi-asserted-by": "publisher", "first-page": "240", "journal-title": "J. Med. Virol.", "key": "B17", "volume": "94", "year": "2022" }, { "DOI": "10.1038/s41586-022-05522-2", "article-title": "The WHO estimates of excess mortality associated with the COVID-19 pandemic", "author": "Msemburi", "doi-asserted-by": "publisher", "first-page": "130", "journal-title": "Nature", "key": "B18", "volume": "613", "year": "2023" }, { "DOI": "10.1080/07391102.2020.1777901", "article-title": "Computational investigation on Andrographis paniculata phytochemicals to evaluate their potency against SARS-CoV-2 in comparison to known antiviral compounds in drug trials", "author": "Murugan", "doi-asserted-by": "publisher", "first-page": "4415", "journal-title": "J. Biomol. Struct. Dyn.", "key": "B19", "volume": "39", "year": "2021" }, { "DOI": "10.1016/S0944-7113(00)80054-9", "article-title": "Pharmacokinetic and oral bioavailability of andrographolide from Andrographis paniculata fixed combination Kan Jang in rats and humans", "author": "Panossian", "doi-asserted-by": "publisher", "first-page": "351", "journal-title": "Phytomedicine", "key": "B20", "volume": "7", "year": "2000" }, { "DOI": "10.1186/1749-8546-8-2", "article-title": "Changes in the contents of four active diterpenoids at different growth stages in Andrographis paniculata (Burm.f.) nees (Chuanxinlian)", "author": "Pholphana", "doi-asserted-by": "publisher", "first-page": "2", "journal-title": "Chin. Med.", "key": "B21", "volume": "8", "year": "2013" }, { "DOI": "10.1016/S2213-2600(20)30527-0", "article-title": "Comparison of the characteristics, morbidity, and mortality of COVID-19 and seasonal influenza: a nationwide, population-based retrospective cohort study", "author": "Piroth", "doi-asserted-by": "publisher", "first-page": "251", "journal-title": "Lancet Respir. Med.", "key": "B22", "volume": "9", "year": "2021" }, { "DOI": "10.1002/pca.3364", "article-title": "Comparison of diterpenoid contents and dissolution profiles of selected Andrographis paniculata crude and extract capsules", "author": "Rangkadilok", "doi-asserted-by": "publisher", "first-page": "1309", "journal-title": "Phytochem. Anal.", "key": "B23", "volume": "35", "year": "2024" }, { "DOI": "10.3390/ph15081013", "article-title": "Efficacy of Kan jang® in patients with mild COVID-19: interim analysis of a randomized, quadruple-blind, placebo-controlled trial", "author": "Ratiani", "doi-asserted-by": "publisher", "first-page": "1013", "journal-title": "Pharmaceuticals", "key": "B24", "volume": "15", "year": "2022" }, { "author": "Rowland", "key": "B25", "volume-title": "Clinical Pharmacokinetics and Pharmacodynamics: Concepts and Applications", "year": "2011" }, { "DOI": "10.1021/acs.jnatprod.0c01324", "article-title": "Anti-SARS-CoV-2 activity of Andrographis paniculata extract and its major component andrographolide in human lung epithelial cells and cytotoxicity evaluation in major organ cell representatives", "author": "Sa-Ngiamsuntorn", "doi-asserted-by": "publisher", "first-page": "1261", "journal-title": "J. Nat. Prod.", "key": "B26", "volume": "84", "year": "2021" }, { "DOI": "10.4103/2229-3485.71856", "article-title": "Sample size estimation in clinical trial", "author": "Sakpal", "doi-asserted-by": "crossref", "first-page": "67", "journal-title": "Perspect. Clin. Res.", "key": "B27", "volume": "1", "year": "2010" }, { "DOI": "10.3389/fphar.2022.952660", "article-title": "A comprehensive review on disposition kinetics and dosage of oral administration of Andrographis paniculata, an alternative herbal medicine, in co-treatment of coronavirus disease", "author": "Songvut", "doi-asserted-by": "publisher", "first-page": "952660", "journal-title": "Front. Pharmacol.", "key": "B28", "volume": "13", "year": "2022" }, { "DOI": "10.1038/s41598-023-28612-1", "article-title": "A validated LC–MS/MS method for clinical pharmacokinetics and presumptive phase II metabolic pathways following oral administration of Andrographis paniculata extract", "author": "Songvut", "doi-asserted-by": "publisher", "first-page": "2534", "journal-title": "Sci. Rep.", "key": "B29", "volume": "13", "year": "" }, { "DOI": "10.3389/fphar.2023.1230401", "article-title": "Comparative pharmacokinetics and safety evaluation of high dosage regimens of Andrographis paniculata aqueous extract after single and multiple oral administration in healthy participants", "author": "Songvut", "doi-asserted-by": "publisher", "first-page": "1230401", "journal-title": "Front. Pharmacol.", "key": "B30", "volume": "14", "year": "" }, { "DOI": "10.1080/13880209.2024.2444446", "article-title": "Non-linear oral bioavailability and clinical pharmacokinetics of high-dose Andrographis paniculata ethanolic extract: relevant dosage implications for COVID-19 treatment", "author": "Songvut", "doi-asserted-by": "publisher", "first-page": "42", "journal-title": "Pharm. Biol.", "key": "B31", "volume": "63", "year": "2025" }, { "DOI": "10.1186/s12879-024-10059-y", "article-title": "Post-viral symptoms and conditions are more frequent in COVID-19 than influenza, but not more persistent", "author": "Tesch", "doi-asserted-by": "publisher", "first-page": "1126", "journal-title": "BMC Infect. Dis.", "key": "B32", "volume": "24", "year": "2024" }, { "DOI": "10.1038/s41564-020-0761-6", "article-title": "Analytical sensitivity and efficiency comparisons of SARS-CoV-2 RT–qPCR primer–probe sets", "author": "Vogels", "doi-asserted-by": "publisher", "first-page": "1299", "journal-title": "Nat. Microbiol.", "key": "B33", "volume": "5", "year": "2020" }, { "DOI": "10.1038/aps.2009.205", "article-title": "Immunomodulatory activity of andrographolide on macrophage activation and specific antibody response", "author": "Wang", "doi-asserted-by": "publisher", "first-page": "191", "journal-title": "Acta Pharmacol. Sin.", "key": "B34", "volume": "31", "year": "2010" }, { "key": "B35", "unstructured": "Clinical management of COVID-19: Interim guidance, 27 may 2020. WHO/2019-nCoV/clinical/2020\n \n 5\n 2020" }, { "DOI": "10.1093/cid/ciaa1280", "article-title": "Viral dynamics and immune correlates of coronavirus disease 2019 (COVID-19) severity", "author": "Young", "doi-asserted-by": "publisher", "first-page": "e2932", "journal-title": "Clin. Infect. Dis.", "key": "B36", "volume": "73", "year": "2021" }, { "DOI": "10.1002/ptr.7141", "article-title": "Efficacy and safety of Xiyanping injection in the treatment of COVID-19: a multicenter, prospective, open-label and randomized controlled trial", "author": "Zhang", "doi-asserted-by": "publisher", "first-page": "4401", "journal-title": "Phytother. Res.", "key": "B37", "volume": "35", "year": "2021" } ], "reference-count": 37, "references-count": 37, "relation": {}, "resource": { "primary": { "URL": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1781740/full" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "Exploratory pharmacokinetic-pharmacodynamic characterization and safety of standardized Andrographis paniculata aqueous extract capsules in patients with mild COVID-19", "type": "journal-article", "update-policy": "https://doi.org/10.3389/crossmark-policy", "volume": "17" }