ArticleAntimicrobial agents and chemotherapy2001
Pharmacokinetic-pharmacodynamic modeling of the electroencephalogram effect of imipenem in healthy rats.
Article in Antimicrobial agents and chemotherapy, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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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
8 citing papers in PubMed, 17 citations in OpenAlex.
- Imipenem in the Rat Brain: A Multidimensional Study on Hippocampal Behavior, GABAergic System, Astrocyte Response, and Neurogenesis.Antibiotics (Basel, Switzerland) · 2026Article
- A Case of Ertapenem Neurotoxicity Resulting in Vocal Tremor and Altered Mentation in a Dialysis Dependent Liver Transplant Patient.Antibiotics (Basel, Switzerland) · 2018Article
- Lack of effect of experimental hypovolemia on imipenem muscle distribution in rats assessed by microdialysis.Antimicrobial agents and chemotherapy · 2005Article
- Microdialysis study of imipenem distribution in skeletal muscle and lung extracellular fluids of noninfected rats.Antimicrobial agents and chemotherapy · 2005Article
- Simultaneous central nervous system distribution and pharmacokinetic-pharmacodynamic modelling of the electroencephalogram effect of norfloxacin administered at a convulsant dose in rats.British journal of pharmacology · 2004Article
- Norfloxacin-induced electroencephalogram alteration and seizures in rats are not triggered by enhanced levels of intracerebral glutamate.Antimicrobial agents and chemotherapy · 2003Article
- Pharmacokinetic-pharmacodynamic modeling of the electroencephalogram effect of norfloxacin in rats.Antimicrobial agents and chemotherapy · 2003Article
- Pharmacokinetic-pharmacodynamic modeling of electroencephalogram effect of imipenem in rats with acute renal failure.Antimicrobial agents and chemotherapy · 2001Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A pharmacokinetic-pharmacodynamic (PK-PD) modeling approach was developed to investigate the epileptogenic activity of imipenem in rats. Initially, animals received an intravenous infusion of imipenem at a rate of 2.65 mg min(-1) for 30 min. Blood samples were collected for drug assay, and an electroencephalogram (EEG) was recorded during infusion and postinfusion. A dramatic delay was observed between concentrations of imipenem in serum and the EEG effect; this effect was accompanied by tremors and partial seizures. Indirect-effect models failed to describe these data, which were successfully fitted using an effect compartment model. The relationship between effect and concentration at the effect site was best described by a spline function. The elimination rate constant from the effect compartment was severalfold lower than that from the central compartment. The robustness of the model was then confirmed after administering the imipenem dose over 60 and 90 min. In conclusion, the successful PK-PD modeling of the imipenem EEG effect in rats constitutes a major improvement for better prediction of the epileptogenic risk associated with this antibiotic.
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