ArticleThe Journal of antimicrobial chemotherapy2022
Population pharmacokinetics of apramycin from first-in-human plasma and urine data to support prediction of efficacious dose.
Article in The Journal of antimicrobial chemotherapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Drug-resistantClinical microbiology reviews · 2025Pooled it
- Membrane-Focused Strategies AgainstAntibiotics (Basel, Switzerland) · 2026Review
- Methodologies for Population Pharmacokinetic Modeling of Target-Site Drug Exposure: A Narrative Review of Current Strategies.Clinical pharmacokinetics · 2026Review
- Enhanced activity of apramycin and apramycin-based combinations against Mycobacteroides abscessus.The Journal of antimicrobial chemotherapy · 2026Article
- Multicentre preclinical profiling of apramycin for the treatment of nontuberculous mycobacteria.EBioMedicine · 2026Article
- A chronic Acinetobacter baumannii pneumonia model to study long-term virulence factors, antibiotic treatments, and polymicrobial infections.Nature communications · 2025Article
- Addressing urgent priorities in antibiotic development: insights from WHO 2023 antibacterial clinical pipeline analyses.The Lancet. Microbe · 2025Review
- Pulmonary Delivery of Antibiotics to the Lungs: Current State and Future Prospects.Pharmaceutics · 2025Review
- Model-informed drug development for antimicrobials: translational pharmacokinetic-pharmacodynamic modelling of apramycin to facilitate prediction of efficacious dose in complicated urinary tract infections.The Journal of antimicrobial chemotherapy · 2025Article
- In vitro activity of apramycin (EBL-1003) in combination with colistin, meropenem, minocycline or sulbactam against XDR/PDR Acinetobacter baumannii isolates from Greece.The Journal of antimicrobial chemotherapy · 2024Article
- In vitro susceptibility of Neisseria gonorrhoeae to netilmicin and etimicin in comparison to gentamicin and other aminoglycosides.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2024Article
- Experimental Determination of the pACS omega · 2024Article
- Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundApramycin is under development for human use as EBL-1003, a crystalline free base of apramycin, in face of increasing incidence of multidrug-resistant bacteria. Both toxicity and cross-resistance, commonly seen for other aminoglycosides, appear relatively low owing to its distinct chemical structure.
objectivesTo perform a population pharmacokinetic (PPK) analysis and predict an efficacious dose based on data from a first-in-human Phase I trial.
methodsThe drug was administered intravenously over 30 min in five ascending-dose groups ranging from 0.3 to 30 mg/kg. Plasma and urine samples were collected from 30 healthy volunteers. PPK model development was performed stepwise and the final model was used for PTA analysis.
resultsA mammillary four-compartment PPK model, with linear elimination and a renal fractional excretion of 90%, described the data. Apramycin clearance was proportional to the absolute estimated glomerular filtration rate (eGFR). All fixed effect parameters were allometrically scaled to total body weight (TBW). Clearance and steady-state volume of distribution were estimated to 5.5 L/h and 16 L, respectively, for a typical individual with absolute eGFR of 124 mL/min and TBW of 70 kg. PTA analyses demonstrated that the anticipated efficacious dose (30 mg/kg daily, 30 min intravenous infusion) reaches a probability of 96.4% for a free AUC/MIC target of 40, given an MIC of 8 mg/L, in a virtual Phase II patient population with an absolute eGFR extrapolated to 80 mL/min.
conclusionsThe results support further Phase II clinical trials with apramycin at an anticipated efficacious dose of 30 mg/kg once daily.
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