ArticlePharmaceutical research2016
Simulation-Based Evaluation of PK/PD Indices for Meropenem Across Patient Groups and Experimental Designs.
Article in Pharmaceutical research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 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.
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Who cites it
40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 61 citations in OpenAlex.
- Systematic review of antimicrobial pharmacokinetic/pharmacodynamic indices in murine thigh and hollow fibre dose fractionation studies analysed with a standard method.The Journal of antimicrobial chemotherapy · 2026Pooled it
- Prolonged Versus Intermittent Infusion of β-Lactam Antibiotics: A Systematic Review and Meta-Regression of Bacterial Killing in Preclinical Infection Models.Clinical pharmacokinetics · 2020Pooled it
- Dosing of Ceftriaxone and Metronidazole for Children With Severe Acute Malnutrition.Clinical pharmacology and therapeutics · 2018Trial
- Plasma and CSF pharmacokinetics of meropenem in neonates and young infants: results from the NeoMero studies.The Journal of antimicrobial chemotherapy · 2018Trial
- Pharmacokinetic/Pharmacodynamic Modelling of Cefquinome in Lactating Sheep and Lactating Goats After Intravenous, Subcutaneous and Long-Acting Administrations.Veterinary sciences · 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
- Drug-resistant gram-negative bacterial infections in children in the Oceania region: review of the epidemiology, antimicrobial availability, treatment, clinical trial and pharmacokinetic data, and key evidence gaps.The Lancet regional health. Western Pacific · 2025Review
- A model-based evaluation of the pharmacokinetics-pharmacodynamics (PKPD) of avibactam in combination with ceftazidime.JAC-antimicrobial resistance · 2025Article
- Simulation-based evaluation of the impact of dose fractionation study design on antibiotic PKPD analyses.JAC-antimicrobial resistance · 2025Article
- Sampling from covariate distribution may not always be necessary in PK/PD simulations: illustrative examples with antibiotics.Journal of pharmacokinetics and pharmacodynamics · 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
- Multistate modeling for survival analysis in critically ill patients treated with meropenem.CPT: pharmacometrics & systems pharmacology · 2024Article
- Translational PK/PD for the Development of Novel Antibiotics-A Drug Developer's Perspective.Antibiotics (Basel, Switzerland) · 2024Review
- Concentrations of Co-Administered Meropenem and Vancomycin in Spinal Tissues Relevant for the Treatment of Pyogenic Spondylodiscitis-An Experimental Microdialysis Study.Antibiotics (Basel, Switzerland) · 2023Article
- PK-PD integration of enrofloxacin and cefquinome alone and in combination againstFrontiers in pharmacology · 2023Article
- Dose Optimization of Meropenem in Patients on Veno-Arterial Extracorporeal Membrane Oxygenation in Critically Ill Cardiac Patients: Pharmacokinetic/Pharmacodynamic Modeling.Journal of clinical medicine · 2022Article
- The area under the effect curve as an efficacy determinant for anti-infectives.CPT: pharmacometrics & systems pharmacology · 2022Article
- Model-Informed Translation of In Vitro Effects of Short-, Prolonged- and Continuous-Infusion Meropenem againstAntibiotics (Basel, Switzerland) · 2022Article
- Why We May Need Higher Doses of Beta-Lactam Antibiotics: Introducing the 'Maximum Tolerable Dose'.Antibiotics (Basel, Switzerland) · 2022Article
- Model-Informed Precision Dosing of Linezolid in Patients with Drug-Resistant Tuberculosis.Pharmaceutics · 2022Article
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 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeAntibiotic dose predictions based on PK/PD indices rely on that the index type and magnitude is insensitive to the pharmacokinetics (PK), the dosing regimen, and bacterial susceptibility. In this work we perform simulations to challenge these assumptions for meropenem and Pseudomonas aeruginosa.
methodsA published murine dose fractionation study was replicated in silico. The sensitivity of the PK/PD index towards experimental design, drug susceptibility, uncertainty in MIC and different PK profiles was evaluated.
resultsThe previous murine study data were well replicated with fT > MIC selected as the best predictor. However, for increased dosing frequencies fAUC/MIC was found to be more predictive and the magnitude of the index was sensitive to drug susceptibility. With human PK fT > MIC and fAUC/MIC had similar predictive capacities with preference for fT > MIC when short t1/2 and fAUC/MIC when long t1/2.
conclusionsA longitudinal PKPD model based on in vitro data successfully predicted a previous in vivo study of meropenem. The type and magnitude of the PK/PD index were sensitive to the experimental design, the MIC and the PK. Therefore, it may be preferable to perform simulations for dose selection based on an integrated PK-PKPD model rather than using a fixed PK/PD index target.
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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.