Evidence map›Paper›PMID 40573427›Full record

ArticleViruses2025

Pharmacokinetics and Metabolism of Broad-Spectrum Antivirals Remdesivir and Obeldesivir with a Consideration to Metabolite GS-441524: Same, Similar, or Different?

Darius Babusis, Cynthia Kim, Jesse Yang, Xiaofeng Zhao, Guoju Geng, Carmen Ip, Nathan Kozon, Hoa Le, Jennifer Leung, Jared Pitts and 7 more

Abstract read
In one paragraph

Article in Viruses, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Darius BabusisGilead Sciences, Inc., Foster City, CA 94404, USA.ORCID 0000-0001-5599-1671
Cynthia KimGilead Sciences, Inc., Foster City, CA 94404, USA.
Jesse YangGilead Sciences, Inc., Foster City, CA 94404, USA.ORCID 0000-0002-6487-1652
Xiaofeng ZhaoGilead Sciences, Inc., Foster City, CA 94404, USA.
Guoju GengGilead Sciences, Inc., Foster City, CA 94404, USA.
Carmen IpGilead Sciences, Inc., Foster City, CA 94404, USA.
Nathan KozonGilead Sciences, Inc., Foster City, CA 94404, USA.
Hoa LeGilead Sciences, Inc., Foster City, CA 94404, USA.
Jennifer LeungGilead Sciences, Inc., Foster City, CA 94404, USA.
Jared PittsGilead Sciences, Inc., Foster City, CA 94404, USA.ORCID 0000-0003-4080-4321
Dustin S SiegelGilead Sciences, Inc., Foster City, CA 94404, USA.ORCID 0009-0008-1365-0287
Rao KallaGilead Sciences, Inc., Foster City, CA 94404, USA.
Bernard MurrayGilead Sciences, Inc., Foster City, CA 94404, USA.
John P BilelloGilead Sciences, Inc., Foster City, CA 94404, USA.
Roy BannisterGilead Sciences, Inc., Foster City, CA 94404, USA.
Richard L MackmanGilead Sciences, Inc., Foster City, CA 94404, USA.ORCID 0000-0001-8861-7205
Raju SubramanianGilead Sciences, Inc., Foster City, CA 94404, USA.ORCID 0000-0002-3806-5227

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

RNA viruses with pandemic potential pose a significant global health risk. The adenosine nucleoside analog GS-441524 is metabolized to its active GS-443902 triphosphate metabolite to inhibit a broad spectrum of RNA viruses. Intravenous (IV) remdesivir (RDV) and oral obeldesivir (ODV) are phosphoramidate and isobutyryl-ester prodrugs of GS-441524, respectively. Following administration, both RDV and ODV show rapid and broad tissue distribution, form the same GS-443902 metabolite in target tissues, and demonstrate promising in vivo efficacy across several RNA virus infection models. In an African green monkey SARS-CoV-2 infection model, respective RDV and ODV treatments yielded similar antiviral efficacy. Here, we compare the in vitro and in vivo pharmacokinetics (PK) and metabolism of RDV and ODV to highlight both similarities and differences in their absorption, metabolism, distribution, and excretion profiles. The distinct route of administration and metabolic fate of each prodrug produced in vivo PK and metabolism profiles with differential GS-441524 to tissue GS-443902 relationships, thereby supporting alternate methods for predicting human efficacious doses. Overall, a metabolism-directed prodrug design enabled optimized delivery of the identical active GS-443902 metabolite through different routes of administration, supporting broader applications of the same nucleoside analog across an expanded spectrum of potential antiviral indications.

Indexed as

AdenosineAdenosine MonophosphateAlanineAntiviral AgentsAnimalsChlorocebus aethiopsCOVID-19COVID-19 Drug TreatmentDisease Models, AnimalHumansProdrugsSARS-CoV-2Tissue DistributionVero CellsAdenosineAdenosine MonophosphateAlanineAntiviral AgentsGS-441524ProdrugsremdesivirantiviralsGS-441524GS-443902obeldesivirpharmacokineticsremdesivir

Identifiers

PMID40573427
PMCPMC12197660

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.