ArticleAntimicrobial agents and chemotherapy2012
Pharmacokinetic/Pharmacodynamic predictors of clinical potency for hepatitis C virus nonnucleoside polymerase and protease inhibitors.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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
20 citing papers in PubMed, 43 citations in OpenAlex.
- Phase I study, and dosing regimen selection for a pivotal COVID-19 trial of GST-HG171.Antimicrobial agents and chemotherapy · 2024Trial
- Safety, Tolerability, and Pharmacokinetics of Intravenous Doses of PF-07304814, a Phosphate Prodrug Protease Inhibitor for the Treatment of SARS-CoV-2, in Healthy Adult Participants.Clinical pharmacology in drug development · 2022Trial
- Innovative Randomized Phase I Study and Dosing Regimen Selection to Accelerate and Inform Pivotal COVID-19 Trial of Nirmatrelvir.Clinical pharmacology and therapeutics · 2022Trial
- Liver-to-plasma vaniprevir (MK-7009) concentration ratios in HCV-infected patients.Antiviral therapy · 2015Trial
- Pharmacokinetics of a three-way drug interaction between danoprevir, ritonavir and the organic anion transporting polypeptide (OATP) inhibitor ciclosporin.Clinical pharmacokinetics · 2013Trial
- Discovery of SARS-CoV-2 papain-like protease (PLScience advances · 2024Article
- A Comprehensive Review of the Clinical Pharmacokinetics, Pharmacodynamics, and Drug Interactions of Nirmatrelvir/Ritonavir.Clinical pharmacokinetics · 2024Review
- Antiviral efficacy of RAY1216 monotherapy and combination therapy with ritonavir in patients with COVID-19: a phase 2, single centre, randomised, double-blind, placebo-controlled trial.EClinicalMedicine · 2023Article
- Preclinical characterization of an intravenous coronavirus 3CL protease inhibitor for the potential treatment of COVID19.Nature communications · 2021Article
- Model-Informed Drug Development for Anti-Infectives: State of the Art and Future.Clinical pharmacology and therapeutics · 2021Review
- A pharmacokinetic/viral kinetic model to evaluate treatment of chronic HCV infection with a non-nucleoside polymerase inhibitor.Antiviral therapy · 2018Article
- Intrahepatic Sampling for the Elucidation of Antiviral Clinical Pharmacology.Clinical pharmacology in drug development · 2017Article
- Quantifying antiviral activity optimizes drug combinations against hepatitis C virus infection.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Modelling hepatitis C therapy--predicting effects of treatment.Nature reviews. Gastroenterology & hepatology · 2015Review
- Characterization of HIV-1 entry inhibitors with broad activity against R5 and X4 viral strains.Journal of translational medicine · 2015Article
- HCV Kinetic Models and Their Implications in Drug Development.CPT: pharmacometrics & systems pharmacology · 2015Review
- Telaprevir-based treatment effects on hepatitis C virus in liver and blood.Hepatology (Baltimore, Md.) · 2014Article
- Treatment of norovirus infections: moving antivirals from the bench to the bedside.Antiviral research · 2014Review
- Discovery of N-[4-[6-tert-butyl-5-methoxy-8-(6-methoxy-2-oxo-1H-pyridin-3-yl)-3-quinolyl]phenyl]methanesulfonamide (RG7109), a potent inhibitor of the hepatitis C virus NS5B polymerase.Journal of medicinal chemistry · 2014Article
- Hepatitis C viral kinetics: the past, present, and future.Clinics in liver disease · 2013Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This analysis was conducted to determine whether the hepatitis C virus (HCV) viral kinetics (VK) model can predict viral load (VL) decreases for nonnucleoside polymerase inhibitors (NNPolIs) and protease inhibitors (PIs) after 3-day monotherapy studies of patients infected with genotype 1 chronic HCV. This analysis includes data for 8 NNPolIs and 14 PIs, including VL decreases from 3-day monotherapy, total plasma trough concentrations on day 3 (C(min)), replicon data (50% effective concentration [EC(50)] and protein-shifted EC(50) [EC(50,PS)]), and for PIs, liver-to-plasma ratios (LPRs) measured in vivo in preclinical species. VK model simulations suggested that achieving additional log(10) VL decreases greater than one required 10-fold increases in the C(min). NNPolI and PI data further supported this result. The VK model was successfully used to predict VL decreases in 3-day monotherapy for NNPolIs based on the EC(50,PS) and the day 3 C(min). For PIs, however, predicting VL decreases using the same model and the EC(50,PS) and day 3 C(min) was not successful; a model including LPR values and the EC(50) instead of the EC(50,PS) provided a better prediction of VL decrease. These results are useful for designing phase 1 monotherapy studies for NNPolIs and PIs by clarifying factors driving VL decreases, such as the day 3 C(min) and the EC(50,PS) for NNPolIs or the EC(50) and LPR for PIs. This work provides a framework for understanding the pharmacokinetic/pharmacodynamic relationship for other HCV drug classes. The availability of mechanistic data on processes driving the target concentration, such as liver uptake transporters, should help to improve the predictive power of the approach.
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