ArticleClinical pharmacology and therapeutics2021
Model-Informed Drug Development for Antimicrobials: Translational PK and PK/PD Modeling to Predict an Efficacious Human Dose for Apramycin.
Article in Clinical pharmacology and therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- What are the optimal pharmacokinetic/pharmacodynamic targets for β-lactamase inhibitors? A systematic review.The Journal of antimicrobial chemotherapy · 2024Pooled it
- Multicentre preclinical profiling of apramycin for the treatment of nontuberculous mycobacteria.EBioMedicine · 2026Article
- Next-generation hybrid bioanalytical platforms and clinical integration of TDM technologies for precision monitoring to optimize last-resort antibiotic therapy.Frontiers in pharmacology · 2026Review
- Exploiting Pharmacokinetic/Pharmacodynamic Methods for Optimizing and Accelerating Drug Development of Innovative Anti-Infectives.ChemMedChem · 2026Review
- Model-based translation of the PKPD-relationship for linezolid and vancomycin on methicillin-resistant Staphylococcus aureus: from in vitro time-kill experiments to a mouse pneumonia model.The Journal of antimicrobial chemotherapy · 2025Article
- Simulation-based evaluation of the impact of dose fractionation study design on antibiotic PKPD analyses.JAC-antimicrobial resistance · 2025Article
- Predicting Antimicrobial Class Specificity of Small Molecules Using Machine Learning.Journal of chemical information and modeling · 2025Article
- 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
- Therapeutic drug monitoring (TDM) of β-lactam/β-lactamase inhibitor (BL/BLI) drug combinations: insights from a pharmacometric simulation study.The Journal of antimicrobial chemotherapy · 2025Article
- Model-based translation of results from in vitro to in vivo experiments for afabicin activity against Staphylococcus aureus.The Journal of antimicrobial chemotherapy · 2024Article
- Machine learning framework to predict pharmacokinetic profile of small molecule drugs based on chemical structure.Clinical and translational science · 2024Article
- Animal Models in Regulatory Breakpoint Determination: Review of New Drug Applications of Approved Antibiotics from 2014-2022.Journal of personalized medicine · 2024Article
- Translational PK/PD for the Development of Novel Antibiotics-A Drug Developer's Perspective.Antibiotics (Basel, Switzerland) · 2024Review
- Translational Pharmacokinetic/Pharmacodynamic Modeling and Simulation of Oxaliplatin and Irinotecan in Colorectal Cancer.Pharmaceutics · 2023Article
- All Roads Lead to Rome: Enhancing the Probability of Target Attainment with Different Pharmacokinetic/Pharmacodynamic Modelling Approaches.Antibiotics (Basel, Switzerland) · 2023Review
- Characterization of antibiotic resistomes by reprogrammed bacteriophage-enabled functional metagenomics in clinical strains.Nature microbiology · 2023Article
- Population pharmacokinetics of apramycin from first-in-human plasma and urine data to support prediction of efficacious dose.The Journal of antimicrobial chemotherapy · 2022Article
- Pharmacokinetic/Pharmacodynamic Modeling and Application in Antibacterial and Antifungal Pharmacotherapy: A Narrative Review.Antibiotics (Basel, Switzerland) · 2022Review
- Predicting Antimicrobial Activity at the Target Site: Pharmacokinetic/Pharmacodynamic Indices versus Time-Kill Approaches.Antibiotics (Basel, Switzerland) · 2021Review
- The Use of Translational Modelling and Simulation to Develop Immunomodulatory Therapy as an Adjunct to Antibiotic Treatment in the Context of Pneumonia.Pharmaceutics · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 5 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Apramycin represents a subclass of aminoglycoside antibiotics that has been shown to evade almost all mechanisms of clinically relevant aminoglycoside resistance. Model-informed drug development may facilitate its transition from preclinical to clinical phase. This study explored the potential of pharmacokinetic/pharmacodynamic (PK/PD) modeling to maximize the use of in vitro time-kill and in vivo preclinical data for prediction of a human efficacious dose (HED) for apramycin. PK model parameters of apramycin from four different species (mouse, rat, guinea pig, and dog) were allometrically scaled to humans. A semimechanistic PK/PD model was developed from the rich in vitro data on four Escherichia coli strains and subsequently the sparse in vivo efficacy data on the same strains were integrated. An efficacious human dose was predicted from the PK/PD model and compared with the classical PK/PD index methodology and the aminoglycoside dose similarity. One-compartment models described the PK data and human values for clearance and volume of distribution were predicted to 7.07 L/hour and 26.8 L, respectively. The required fAUC/MIC (area under the unbound drug concentration-time curve over MIC ratio) targets for stasis and 1-log kill in the thigh model were 34.5 and 76.2, respectively. The developed PK/PD model predicted the efficacy data well with strain-specific differences in susceptibility, maximum bacterial load, and resistance development. All three dose prediction approaches supported an apramycin daily dose of 30 mg/kg for a typical adult patient. The results indicate that the mechanistic PK/PD modeling approach can be suitable for HED prediction and serves to efficiently integrate all available efficacy data with potential to improve predictive capacity.
Indexed as
Identifiers
What 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.