ArticleAntimicrobial agents and chemotherapy2012
Comparative pharmacodynamics of the new oxazolidinone tedizolid phosphate and linezolid in a neutropenic murine Staphylococcus aureus pneumonia model.
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 24 papers.
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Who cites it
24 citing papers in PubMed, 53 citations in OpenAlex.
- Effect of food on the pharmacokinetic characteristics of a single oral dose of LCB01-0371, a novel oxazolidinone antibiotic.Drug design, development and therapy · 2018Trial
- In vitro, in vivo, and clinical studies of tedizolid to assess the potential for peripheral or central monoamine oxidase interactions.Antimicrobial agents and chemotherapy · 2013Trial
- [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Advances in Therapeutic Drug Monitoring and Pharmacokinetic Researches of Oxazolidinone Antibacterial Agents in the Elderly Patients.Clinical interventions in aging · 2026Review
- Methicillin-resistantThe Lancet regional health. Western Pacific · 2025Review
- Translational predictions of phase 2a first-in-patient efficacy studies for antituberculosis drugs.The European respiratory journal · 2023Article
- Antibiotic-Derived Radiotracers for Positron Emission Tomography: Nuclear or "Unclear" Infection Imaging?Angewandte Chemie (International ed. in English) · 2022Review
- Pharmacokinetics and Pharmacodynamics of Tedizolid.Clinical pharmacokinetics · 2022Review
- Population Pharmacokinetics, Exposure-Response, and Probability of Target Attainment Analyses for Tedizolid in Adolescent Patients with Acute Bacterial Skin and Skin Structure Infections.Antimicrobial agents and chemotherapy · 2021Article
- Telacebec (Q203)-containing intermittent oral regimens sterilized mice infected with Mycobacterium ulcerans after only 16 doses.PLoS neglected tropical diseases · 2020Article
- Radiosynthesis and Biodistribution ofACS infectious diseases · 2020Article
- Article
- Efficacy of Tedizolid against Enterococci and Staphylococci, IncludingAntimicrobial agents and chemotherapy · 2019Article
- In vivo pharmacodynamics of lefamulin, the first systemic pleuromutilin for human use, in a neutropenic murine thigh infection model.The Journal of antimicrobial chemotherapy · 2019Article
- Article
- Article
- Comparative In Vivo Efficacies of Tedizolid in Neutropenic versus Immunocompetent Murine Streptococcus pneumoniae Lung Infection Models.Antimicrobial agents and chemotherapy · 2017Article
- Linezolid for Infants and Toddlers With Disseminated Tuberculosis: First Steps.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2016Article
- Tedizolid Phosphate: a Next-Generation Oxazolidinone.Infectious diseases and therapy · 2015Article
- In vivo pharmacokinetics and pharmacodynamics of the lantibiotic NAI-107 in a neutropenic murine thigh infection model.Antimicrobial agents and chemotherapy · 2015Article
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
Tedizolid phosphate (TR-701) is a novel oxazolidinone prodrug (converted to the active form tedizolid [TR-700]) with potent Staphylococcus aureus activity. The current studies characterized and compared the in vivo pharmacokinetic/pharmacodynamic (PD) characteristics of TR-701/TR-700 and linezolid against methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in the neutropenic murine pneumonia model. The pharmacokinetic properties of both drugs were linear over a dose range of 0.625 to 40 mg/kg of body weight. Protein binding was 30% for linezolid and 85% for TR-700. Mice were infected with one of 11 isolates of S. aureus, including MSSA and community- and hospital-acquired MRSA strains. Each drug was administered by oral-gastric gavage every 12 h (q12h). The dosing regimens ranged from 1.25 to 80 mg/kg/12 h for linezolid and 0.625 to 160 mg/kg/12 h for TR-701. At the start of therapy, mice had 6.24 ± 0.40 log(10) CFU/lungs, which increased to 7.92 ± 1.02 log(10) CFU/lungs in untreated animals over a 24-h period. A sigmoid maximum-effect (E(max)) model was used to determine the antimicrobial exposure associated with net stasis (static dose [SD]) and 1-log-unit reduction in organism relative to the burden at the start of therapy. The static dose pharmacodynamic targets for linezolid and TR-700 were nearly identical, at a free drug (non-protein-bound) area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC ratio) of 19 and 20, respectively. The 1-log-unit kill endpoints were also similar, at 46.1 for linezolid and 34.6 for TR-700. The exposure targets were also comparable for both MSSA and MRSA isolates. These dosing goals support further clinical trial examination of TR-701 in MSSA and MRSA pneumonia.
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