ArticleClinical pharmacokinetics2013
The clinical relevance of plasma protein binding changes.
Article in Clinical pharmacokinetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 4 of them syntheses that pooled it.
What it found
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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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
121 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Re-discover the value of protein binding assessments in hepatic and renal impairment studies and its contributions in drug labels and dose decisions.Clinical and translational science · 2024Pooled it
- Clinical practice guidelines for therapeutic drug monitoring of teicoplanin: a consensus review by the Japanese Society of Chemotherapy and the Japanese Society of Therapeutic Drug Monitoring.The Journal of antimicrobial chemotherapy · 2022Guideline
- An Overview of the Protein Binding of Cephalosporins in Human Body Fluids: A Systematic Review.Frontiers in pharmacology · 2022Pooled it
- Optimization of the treatment with beta-lactam antibiotics in critically ill patients-guidelines from the French Society of Pharmacology and Therapeutics (Société Française de Pharmacologie et Thérapeutique-SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (Société Française d'Anesthésie et Réanimation-SFAR).Critical care (London, England) · 2019Guideline
- Phase 1, randomized, double-blind, placebo-controlled, ascending single- and multiple-dose study of the safety, tolerability, and pharmacokinetics of intravenous xeruborbactam (QPX7728) in healthy adult subjects.Antimicrobial agents and chemotherapy · 2025Trial
- Validation of Cefiderocol Package Insert Dosing Recommendation for Patients Receiving Continuous Renal Replacement Therapy: A Prospective Multicenter Pharmacokinetic Study.Open forum infectious diseases · 2024Trial
- Plasma protein binding of ceftriaxone in critically ill patients: can we predict unbound fractions?The Journal of antimicrobial chemotherapy · 2023Trial
- High-Dose Ceftriaxone for Bacterial Meningitis and Optimization of Administration Scheme Based on Nomogram.Antimicrobial agents and chemotherapy · 2019Trial
- Effect of Hepatic Impairment on the Pharmacokinetics of Pradigastat, a Diacylglycerol Acyltransferase 1 (DGAT1) Inhibitor.Clinical pharmacokinetics · 2015Trial
- Phytochemical Profiling, In Vitro α-Amylase Inhibitory and Antioxidant Activities ofPlants (Basel, Switzerland) · 2026Article
- Membrane-Dependent Adsorption of Lacosamide in CRRT: Implications for Drug Dosing in Critically Ill Renal Patients.Medical science monitor : international medical journal of experimental and clinical research · 2026Article
- Protein Binding of Cefazolin is Not Saturated in Human Synovial Fluid After Single-Dose Perioperative Antibiotic Prophylaxis.European journal of drug metabolism and pharmacokinetics · 2026Article
- The "obesity paradox" in dosing: a comprehensive analytical review of cockcroft-gault versus CKD-EPI for predicting clearance of narrow-therapeutic-index drugs in patients with BMI > 40 kg/m².European journal of clinical pharmacology · 2026Review
- Article
- Radiolabeled Antimicrobials for Infection Imaging: A Scoping Review.International journal of molecular sciences · 2026Article
- Predictors and nomogram of midazolam-induced somnolence: a retrospective cohort study.BMC anesthesiology · 2026Article
- Effects of extracorporeal membrane oxygenation and/or renal replacement therapy on piperacillin/tazobactam levels in critically ill patients.Frontiers in pharmacology · 2026Article
- Physiologically based pharmacokinetic modeling and dose adjustment of imipenem in pediatric patients with renal impairment.Frontiers in cellular and infection microbiology · 2026Article
- Low Target Attainment of Intravenous Cefuroxime in Critically Ill Term Neonates and Children: A Pooled Population Pharmacokinetics Study.Clinical pharmacokinetics · 2026Article
- Investigation of the Binding of the Macrolide Antibiotic Telithromycin to Human Serum Albumin by NMR Spectroscopy.International journal of molecular sciences · 2025Article
61 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Controversy reigns as to how protein binding changes alter the time course of unbound drug concentrations in patients. Given that the unbound concentration is responsible for drug efficacy and potential drug toxicity, this area is of significant interest to clinicians and academics worldwide. The present uncertainty means that many questions relating to this area exist, including "How important is protein binding?", "Is protein binding always constant?", "Do pH and temperature changes alter binding?" and "How do protein binding changes affect dosing requirements?". In this paper, we seek to address these questions and consider the data associated with altered pharmacokinetics in the presence of changes in protein binding and the clinical consequences that these may have on therapy, using examples from the critical care area. The published literature consistently indicates that a change in the protein binding and unbound concentrations of some drugs are common in certain specific patient groups such as the critically ill. Changes in pharmacokinetic parameters, including clearance and apparent volume of distribution (V(d)), may be dramatic. Drugs with high protein binding, high intrinsic clearance (e.g. clearance by glomerular filtration) and where dosing is not titrated to effect are most likely to be affected in a clinical context. Drugs such as highly protein bound antibacterials with multiple half-lives within a dosing interval and that have some level of renal clearance, such as ertapenem, teicoplanin, ceftriaxone and flucloxacillin, are commonly affected. In response to these challenges, clinicians need to adapt dosing regimens rationally based on the pharmacokinetic/pharmacodynamic characteristics of the drug. We propose that further pharmacokinetic modelling-based research is required to enable the design of robust dosing regimens for drugs affected by altered protein binding.
Indexed as
Identifiers
23150213What OpenQuestion holds
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.