ArticleAntimicrobial agents and chemotherapy2008
Effect of protein binding on the pharmacological activity of highly bound antibiotics.
Article in Antimicrobial agents and chemotherapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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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.
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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
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 113 citations in OpenAlex.
- Antibiotic-Loaded Platelet-Rich Fibrin (AL-PRF) as a New Carrier for Antimicrobials: A Systematic Review of In Vitro Studies.International journal of molecular sciences · 2025Pooled it
- Development of a physiology-directed population pharmacokinetic and pharmacodynamic model for characterizing the impact of genetic and demographic factors on clopidogrel response in healthy adults.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2016Trial
- Article
- Misconceptions among medicinal chemists regarding ADME and PK optimization.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Article
- The Changing Landscape of Antibiotic Treatment: Reevaluating Treatment Length in the Age of New Agents.Antibiotics (Basel, Switzerland) · 2025Review
- Article
- Interaction of Cephalosporins with Human Serum Albumin: A Structural Study.Journal of medicinal chemistry · 2024Article
- Interspecies variability in protein binding of antibiotics basis for translational PK/PD studies-a case study using cefazolin.Antimicrobial agents and chemotherapy · 2024Article
- Article
- Deriving protein binding-corrected chemical concentrations for in vitro testing.Clinical and translational science · 2023Article
- Biased computation of probability of target attainment for antimicrobial drugs.CPT: pharmacometrics & systems pharmacology · 2023Article
- Target attainment and population pharmacokinetics of flucloxacillin in critically ill patients: a multicenter study.Critical care (London, England) · 2023Observational
- Protein Binding in Translational Antimicrobial Development-Focus on Interspecies Differences.Antibiotics (Basel, Switzerland) · 2022Review
- Molecular Basis of Interactions between the Antibiotic Nitrofurantoin and Human Serum Albumin: A Mechanism for the Rapid Drug Blood Transportation.International journal of molecular sciences · 2021Article
- Fetal bovine serum albumin inhibits antimicrobial peptide activity and binds drug only in complex with α1-antitrypsin.Scientific reports · 2021Article
- Albumin in Tears Modulates Bacterial Susceptibility to Topical Antibiotics in Ophthalmology.Frontiers in medicine · 2021Article
- Paclitaxel, Imatinib and 5-Fluorouracil Increase the Unbound Fraction of Flucloxacillin In Vitro.Antibiotics (Basel, Switzerland) · 2020Article
- The Antistaphylococcal Lysin, CF-301, Activates Key Host Factors in Human Blood To Potentiate Methicillin-ResistantAntimicrobial agents and chemotherapy · 2019Article
- Effects of Microplate Type and Broth Additives on Microdilution MIC Susceptibility Assays.Antimicrobial agents and chemotherapy · 2019Article
- Combination of Antibodies and Antibiotics as a Promising Strategy Against Multidrug-Resistant Pathogens of the Respiratory Tract.Frontiers in immunology · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During antibiotic drug development, media are frequently spiked with either serum/plasma or protein supplements to evaluate the effect of protein binding. Usually, previously reported serum or plasma protein binding values are applied in the analysis. The aim of this study was to evaluate this approach by experimentally measuring free, unbound concentrations for antibiotics with reportedly high protein binding and their corresponding antimicrobial activities in media containing commonly used protein supplements. Free, unbound ceftriaxone and ertapenem concentrations were determined in bacterial growth medium with and without bovine/human serum albumin, as well as adult bovine serum and human plasma using in vitro microdialysis. The corresponding antimicrobial activity was determined in MIC and time-kill curve experiments using Escherichia coli ATCC 25922 and Streptococcus pneumoniae ATCC 6303 as test strains. A semimechanistic maximum effect model was simultaneously fitted to the data and respective EC(50) (concentration at half-maximum effect) values compared. Protein binding differed significantly for ceftriaxone (P < 0.05) between human plasma (76.8 +/- 11.0%) and commercially available bovine (20.2 +/- 8.3%) or human serum albumin (56.9 +/- 16.6%). Similar results were obtained for ertapenem (human plasma, 73.8 +/- 11.6%; bovine serum albumin, 12.4 +/- 4.8%; human serum albumin, 17.8 +/- 11.5%). The MICs and EC(50)s of both strains were significantly increased (P < 0.05) for ceftriaxone when comparing human and bovine serum albumin, whereas the EC(50)s were not significantly different for ertapenem. Free, unbound antibiotic concentrations differed substantially between plasma and protein supplements and correlated well with antimicrobial efficacy. Therefore, free, active concentrations should be measured in the test system instead of correcting for literature protein binding values.
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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.