ArticleAntimicrobial agents and chemotherapy2005
Pharmacokinetic modeling of free amoxicillin concentrations in rat muscle extracellular fluids determined by microdialysis.
Article in Antimicrobial agents and chemotherapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis 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.
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Who cites it
4 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Dynamic distribution of systemically administered antibiotics in orthopeadically relevant target tissues and settings.APMIS : acta pathologica, microbiologica, et immunologica Scandinavica · 2024Pooled it
- PK/PD-Guided Strategies for Appropriate Antibiotic Use in the Era of Antimicrobial Resistance.Antibiotics (Basel, Switzerland) · 2025Review
- Pulmonary Pharmacokinetic and Pharmacodynamic Evaluation of Ampicillin/Sulbactam Regimens for Pneumonia Caused by Various Bacteria, includingAntibiotics (Basel, Switzerland) · 2023Article
- Lack of effect of experimental hypovolemia on imipenem muscle distribution in rats assessed by microdialysis.Antimicrobial agents and chemotherapy · 2005Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aim of the present study was to investigate amoxicillin (AMX) distribution in muscle interstitial fluid by microdialysis in healthy, awake rats. Microdialysis probes were inserted into the jugular vein and hind leg muscle. Probe recoveries in each rat were determined by retrodialysis with cefadroxil. AMX was administered as a bolus dose of 50 mg.kg(-1), and microdialysis samples were collected during 180 min. Concentrations of unbound drug in blood and muscle were analyzed simultaneously by a population approach. Simulations were conducted using a hybrid, physiologically based pharmacokinetic model to investigate the potential impact of tissue blood flow on muscle AMX distribution. A two-compartment pharmacokinetic model described adequately the unbound amoxicillin concentration-time profiles in blood and muscle. Muscle AMX distribution equilibrium was rapidly achieved. Consequently, the best results were obtained by considering concentrations in muscle as part of the central compartment. The ratio of the concentration of unbound drug in muscle to that in blood (Rmodel) was estimated to 0.80 by the model, which is close to the mean value obtained by noncompartmental data analysis (Rarea= 0.86 +/- 0.29). Simulations conducted with a hybrid, physiologically based pharmacokinetic model suggest that a muscle blood flow reduction of 30% to 50%, such as could be encountered in critical care patients, has virtually no effect on muscle AMX concentration profiles. In conclusion, this study has clearly demonstrated that AMX distributes rapidly and extensively within muscle interstitial fluid, consistent with theory, and that altered muscle blood flow seems unlikely to have a major effect on these distribution characteristics.
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