Evidence map›Paper›PMID 25822283›Full record

ReviewClinical pharmacokinetics2015

Pharmacokinetic, Pharmacodynamic, and Drug-Interaction Profile of the Hepatitis C Virus NS5B Polymerase Inhibitor Sofosbuvir.

Brian J Kirby, William T Symonds, Brian P Kearney, Anita A Mathias

2 registry-linked trialsAbstract readReview
PubMed Publisher
In one paragraph

Review in Clinical pharmacokinetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 96 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
96citing papers in PubMed, 2 pooled it
15.6field-weighted citation impact, top 1% of its field
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.

NCT03883698 phase3completednot on this mapstarted 2019, after this paper: background citation

Pharmacokinetics of Low-dose Sofosbuvir in Dialysis-dependent Patients With Hepatitis C Virus Infection

TypeinterventionalSponsorSanjay Gandhi Postgraduate Institute of Medical SciencesRan2019 to 2020Enrolled30ConditionsKidney Failure, Chronic, Hepatitis CArmsSofosbuvir, Daclatasvir 60 mg
NCT04382404 phase1completednot on this mapstarted 2020, after this paper: background citation

Phase 1 Pharmacokinetic Trial of Sofosbuvir/Velpatasvir in Pregnant Women With Chronic Hepatitis C Virus Infection

TypeinterventionalSponsorCatherine Anne ChappellRan2020 to 2023Enrolled11ConditionsHepatitis C, ChronicArmsSofosbuvir-Velpatasvir Drug Combination
3 · Its place in the literature

Who cites it

96 citing papers in PubMed, 2 syntheses or guidelines pooled it, 239 citations in OpenAlex.

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  16. Antivirals in COVID-19: A Focus on Pediatric Cardiac Patients.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2025
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36 more citing papers are in PubMed but not listed here.

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

4 authors at 1 institution in 1 country.

Brian J KirbyGilead Sciences Inc., 333 Lakeside Drive, Foster City, CA, 94404, USA.
William T Symonds
Brian P Kearney
Anita A Mathias
Gilead Sciences (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Sofosbuvir (SOVALDI(®)), a potent, once-daily, orally administered nucleotide analog prodrug inhibitor of the hepatitis C virus (HCV) NS5B polymerase is approved in the USA, EU, Canada, and other regions for the treatment of HCV infection as a component of an antiviral treatment regimen. Sofosbuvir undergoes intracellular activation to form GS-461203 (active triphosphate, not detected in plasma), and ultimately the inactive, renally eliminated metabolite GS-331007. GS-331007 was identified as the primary analyte of interest for clinical pharmacology studies as it accounted for >90 % of systemic drug-related material exposure, and provided comparable exposure-response relationships for viral kinetics as observed for sofosbuvir. GS-331007 and sofosbuvir exhibit linear pharmacokinetics with minimal accumulation upon multiple dosing. Compared to healthy subjects, HCV-infected patients had modestly lower (39 %) GS-331007 area under the plasma concentration-time curve (AUC) and higher sofosbuvir AUC (60 %). Sofosbuvir can be administered without dose modification in HCV-infected patients with any degree of hepatic impairment or mild to moderate renal impairment. Sofosbuvir has a low propensity for clinically significant drug interactions with common concomitant medications used by HCV-infected patients. Clinically significant alterations in GS-331007 or sofosbuvir exposures are limited to potent inducers of intestinal P-glycoprotein that may lower exposure. In HCV-infected patients, demographic variables do not significantly influence GS-331007 and sofosbuvir exposures and no consistent exposure-response relationships were observed for efficacy or safety. This review focuses on the clinical pharmacokinetics, pharmacodynamics, and pharmacokinetic-pharmacodynamic relationships of sofosbuvir, and summarizes a number of drug interaction studies with important concomitant medications commonly used by HCV-infected patients.

Indexed as

AnimalsAntiviral AgentsDrug InteractionsHepatitis C, ChronicHumansProdrugsRNA-Dependent RNA PolymeraseSofosbuvirViral Nonstructural ProteinsAntiviral AgentsNS-5 protein, hepatitis C virusProdrugsRNA-Dependent RNA PolymeraseSofosbuvirViral Nonstructural Proteins

Identifiers

PMID25822283
OpenAlexW2068062063

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.