Remdesivir is an antiviral prodrug that, upon intravenous
administration, is rapidly distributed and metabolized
intracellularly to its active triphosphate form, which inhibits
viral RNA-dependent RNA polymerase, thereby blocking viral
replication. Pharmacokinetically, remdesivir exhibits a short
plasma half-life due to rapid hydrolysis and metabolism, typically
modeled by a two- or multi-compartment model to account for its
rapid distribution and sequential formation of metabolites such as
GS-441524, which has a longer half-life and contributes to
sustained antiviral activity. Due to its prodrug nature, remdesivir
demonstrates a high volume of distribution, reflecting extensive
tissue penetration, and requires intravenous dosing as its oral
bioavailability is poor. Pharmacodynamically, remdesivir acts by
mimicking adenosine nucleotides, incorporating into viral RNA, and
causing premature chain termination, with clinical efficacy
demonstrated primarily against RNA viruses like SARS-CoV-2.
2-compartment model with remdesivir and metabolites GS_704277
and active GS_441524
each metabolite modelled as 2 compartment model interconnected
via central and peripheral clearance as estimated in [1]
Simulation of concentration of remdesivir and metabolites in 5
days, remdesivir administered once daily as 200 mg intravenous
infusion.
References:
[1] Abouellil, A., Bilal, M., Taubert, M. et al. A
population pharmacokinetic model of remdesivir and its major
metabolites based on published mean values from healthy subjects.
Naunyn-Schmiedeberg's Arch Pharmacol 396, 73–82 (2023).
https://doi.org/10.1007/s00210-022-02292-6
[2] https://go.drugbank.com/drugs/DB14761
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