modelComponentRemdesivirPKPD

As Remdesivir bioavailability is almost 0 it is not fit for oral administration, thus intravenous administration is recommended first dose 200mg and other 4 - 10 doses per 100 mg every 24 h with intravenous application typically 30-60 minutes. 

RDV is taken by target cell and metabolized in multiple steps (utilizing enzymes hydrolaze, phosphataze) to form active form GS-443902. It is also metabolised (nucleotidase) to nonactive form GS-441524. 

Critical is concentration of active form in target cells.

RDV, active and non_active have different clearance rate elimination by kidneys/liver.

[1] Li, R., Liclican, A., Xu, Y., Pitts, J., Niu, C., Zhang, J., Kim, C., Zhao, X., Soohoo, D., Babusis, D., Yue, Q., Ma, B., Murray, B. P., Subramanian, R., Xie, X., Zou, J., Bilello, J. P., Li, L., Schultz, B. E., … Feng, J. Y. (2021). Key metabolic enzymes involved in Remdesivir activation in human lung cells. Antimicrobial Agents and Chemotherapy, 65(9). https://doi.org/10.1128/AAC.00602-21

[2] Humeniuk, R., Mathias, A., Cao, H., Osinusi, A., Shen, G., Chng, E., Ling, J., Vu, A., & German, P. (2020). Safety, Tolerability, and Pharmacokinetics of Remdesivir, An Antiviral for Treatment of COVID-19, in Healthy Subjects. Clinical and Translational Science, 13(5), 896–906. https://doi.org/10.1111/cts.12840