In Silico Prediction of Andrographolide Dosage Regimens for COVID-19 Treatment
Teerachat Saeheng, Juntra Karbwang, Kesara Na-Bangchang
The American Journal of Chinese Medicine, doi:10.1142/s0192415x22500732
Andrographolide (APE) has been used for COVID-19 treatment in various clinical settings in South-East Asia due to its benefits on reduction of viral clearance and prevention of disease progression. However, the limitation of APE clinical use is the high incidence of adverse events. The objective of this study was to find the optimal dosage regimens of APE for COVID-19 treatment. The whole-body physiologically-based pharmacokinetic (PBPK) models were constructed using data from the published articles and validated against clinical observations. The inhibitory effect of APE was determined for the potency of drug efficacy. For prevention of pneumonia, multiple oral doses such as 120 mg for three doses, followed by 60 mg three times daily for 4 consecutive days, or 200 mg intravenous infusion at the rate of 20 mg/h once daily is advised in patients with mild COVID-19. For prevention of pneumonia and reduction of viral clearance time, the recommended dosage regimen is 500 mg intravenous infusion at the rate of 25 mg/h once daily in patients with mild-tomoderate COVID-19. One hundred virtual populations (50 males and 50 females) were simulated for oral and intravenous infusion formulations of APE. The eligible PBPK/PD models successfully predicted optimal dosage regimens and formulations of APE for prevention of disease progression and/or reduction of viral clearance time. Additionally, APE should be co-administered with other antiviral drugs to enhance therapeutic efficacy for COVID-19 treatment.
Cholangiocarcinoma (No. 1/2556 , dated 12 October 2013 ), and the National Research Council of Thailand (No. 45/2561 , dated 10 September 2018) . K.N. was supported by the National Research Council of Thailand under the Research Team Promotion grant (grant number NRCT 820/2563, dated 12 November 2020).
Supplementary Information
References
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"abstract": "<jats:p> Andrographolide (APE) has been used for COVID-19 treatment in various clinical settings in South-East Asia due to its benefits on reduction of viral clearance and prevention of disease progression. However, the limitation of APE clinical use is the high incidence of adverse events. The objective of this study was to find the optimal dosage regimens of APE for COVID-19 treatment. The whole-body physiologically-based pharmacokinetic (PBPK) models were constructed using data from the published articles and validated against clinical observations. The inhibitory effect of APE was determined for the potency of drug efficacy. For prevention of pneumonia, multiple oral doses such as 120[Formula: see text]mg for three doses, followed by 60[Formula: see text]mg three times daily for 4 consecutive days, or 200[Formula: see text]mg intravenous infusion at the rate of 20 mg/h once daily is advised in patients with mild COVID-19. For prevention of pneumonia and reduction of viral clearance time, the recommended dosage regimen is 500[Formula: see text]mg intravenous infusion at the rate of 25[Formula: see text]mg/h once daily in patients with mild-to-moderate COVID-19. One hundred virtual populations (50 males and 50 females) were simulated for oral and intravenous infusion formulations of APE. The eligible PBPK/PD models successfully predicted optimal dosage regimens and formulations of APE for prevention of disease progression and/or reduction of viral clearance time. Additionally, APE should be co-administered with other antiviral drugs to enhance therapeutic efficacy for COVID-19 treatment. </jats:p>",
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