Trial reportAntimicrobial agents and chemotherapy2013
Pharmacokinetics, safety, and tolerability of GS-9851, a nucleotide analog polymerase inhibitor for hepatitis C virus, following single ascending doses in healthy subjects.
Trial report in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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Who cites it
18 citing papers in PubMed, 38 citations in OpenAlex.
- Pharmacokinetic interaction between atorvastatin and fixed-dose combination of sofosbuvir/ledipasvir in healthy male Egyptian volunteers.European journal of clinical pharmacology · 2021Trial
- Lack of clinically important PK interaction between coformulated ledipasvir/sofosbuvir and rilpivirine/emtricitabine/tenofovir alafenamide.Pharmacology research & perspectives · 2017Trial
- Pharmacokinetics, pharmacodynamics, and tolerability of GS-9851, a nucleotide analog polymerase inhibitor, following multiple ascending doses in patients with chronic hepatitis C infection.Antimicrobial agents and chemotherapy · 2013Trial
- Comparative Pharmacology of a Bis-Pivaloyloxymethyl Phosphonate Prodrug Inhibitor of Enolase after Oral and Parenteral Administration.ACS pharmacology & translational science · 2023Article
- The Inhibitory Potential of 2'-dihalo Ribonucleotides against HCV: Molecular Docking, Molecular Simulations, MM-BPSA, and DFT Studies.Molecules (Basel, Switzerland) · 2022Article
- Phosphoryl Prodrugs: Characteristics to Improve Drug Development.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2022Article
- An evaluation of ledipasvir + sofosbuvir for the treatment of chronic hepatitis C infection.Expert opinion on pharmacotherapy · 2021Review
- Toward a Molecular Basis of Cellular Nucleoside Transport in Humans.Chemical reviews · 2021Review
- RNA-dependent RNA polymerase (RdRp) inhibitors: The current landscape and repurposing for the COVID-19 pandemic.European journal of medicinal chemistry · 2021Review
- Antiviral and Antimicrobial Nucleoside Derivatives: Structural Features and Mechanisms of Action.Molecular biology · 2021Article
- A Pharmacology Perspective of Simultaneous Tuberculosis and Hepatitis C Treatment.Antimicrobial agents and chemotherapy · 2019Review
- The ProTide Prodrug Technology: From the Concept to the Clinic.Journal of medicinal chemistry · 2018Review
- Pharmacologic Considerations in the Treatment of Hepatitis C Virus in Persons With HIV.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2016Review
- Validation and Application of a Liquid Chromatography-Tandem Mass Spectrometry Method To Determine the Concentrations of Sofosbuvir Anabolites in Cells.Antimicrobial agents and chemotherapy · 2015Article
- Sofosbuvir for treatment of chronic hepatitis C.Hepatology international · 2015Review
- Changing the face of hepatitis C management - the design and development of sofosbuvir.Drug design, development and therapy · 2015Review
- Sofosbuvir: a new oral once-daily agent for the treatment of hepatitis C virus infection.P & T : a peer-reviewed journal for formulary management · 2014Article
- Chutes and ladders in hepatitis C nucleoside drug development.Antiviral research · 2014Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To investigate the pharmacokinetics, safety, and tolerability of GS-9851 (formerly PSI-7851), a new nucleotide analog inhibitor of hepatitis C virus (HCV), we conducted a double-blind, parallel, placebo-controlled, randomized, single-ascending-dose study. Healthy subjects received oral doses of 25 to 800 mg GS-9851. Peak concentrations of GS-9851 in plasma were achieved more rapidly than those of the metabolites GS-566500 (formerly PSI-352707) and GS-331007 (formerly PSI-6206), with time to maximum concentration of drug in plasma (t(max)) values of 1.0 to 1.8 h, 1.5 to 3.0 h, and 3.0 to 6.0 h, respectively. The majority of systemic drug exposure was from the nucleoside GS-331007, with maximum concentration of drug in plasma (C(max)) and area under the concentration-time curve to the last measurable concentration (AUC(0-t)) values at least 7- and 41-fold higher, respectively, than those obtained for GS-9851 after adjusting for differences in molecular weight. The terminal elimination half-life (t(1/2)) of GS-331007 increased with the dose, achieving a t(1/2) of 25.7 h at 800 mg GS-9851. Dose proportionality was not observed for GS-331007. The majority of drug recovered in urine was in the form of GS-331007, with the percentage of this metabolite in urine samples ranging from 57% to 27% with increasing dose. GS-9851 was generally well tolerated, with no maximum tolerated dose identified. In conclusion, GS-9851 and its metabolites demonstrated a favorable pharmacokinetic profile consistent with once-daily dosing, and therefore, further clinical studies evaluating GS-9851 in HCV-infected patients are warranted.
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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.