Effects of some quinolones on imipenem-induced seizures in DBA/2 mice

Sarro, Angela De; Ammendola, D.; Sarro, Giovambattista De

doi:10.1016/0306-3623(94)90068-x

Cited by 21 publications

(13 citation statements)

References 41 publications

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“…The potential risk of PEF treatment increased when it was simultaneously administered with aminophyllins or nonsteroidal antiinflammatory drugs (Christ et al, 1988;Segev et al, 1988;Norrby, 1991). These clinical findings are in accordance with the results of animal experiments, when the proconvulsant activity of the FQAs was demonstrated in an epileptic model and the intraperitoneal administration of PEF-induced seizures in mice (De Sarro et al, 1994;De Sarro et al, 1997). Direct excitatory effect of PEF treatment was demonstrated in vitro on the CA1 region of the rat hippocampus (Dimpfel et al, 1991).…”

Section: Modification Of Innervation In Salivary Glandsupporting

confidence: 65%

Modification of Innervation Pattern by Fluoroquinolone Treatment in the Rat Salivary Glands

Kelentey

Deák

Zelles

et al. 2010

The Anatomical Record

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Fluoroquinolone antibiotics (FQAs) are widely used in dental and medical therapy. Despite their known severe adverse actions on the central and peripheral nervous system, little attention has been directed toward the potential toxic side effects of these compounds on the oral tissues. As the saliva secretion is controlled by the nervous system and neuropeptides, the neurotoxic effect of pefloxacin (PEF), a representative member of FQAs, was studied in rats in the present work. Previously, we demonstrated a significant weight loss of parotid gland tissue, a marked decrease in 3H-thymidine incorporation, a decreased volume of saliva and amylase activity of the glandular tissue in response to PEF. Animals received intraperitoneal injection of PEF (20 mg/100 g body weight daily) for 3 and 7 days. Normal histology, and neurofilament 200, substance P (SP) and calcitonin gene-related polypeptide (CGRP) containing nerve fibers were detected with immunohistochemical methods. A marked decrease of the weights in salivary glands and the acinar diameters were measured. Similarly, a strong and significant decrease of the number of SP and CGRP containing nerve fibers were detected. These findings suggest that the impaired morphology and innervation pattern of salivary glands is related to the neurotoxic adverse effect of FQA treatment. Anat Rec,

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Section: Modification Of Innervation In Salivary Glandsupporting

confidence: 65%

Modification of Innervation Pattern by Fluoroquinolone Treatment in the Rat Salivary Glands

Kelentey

Deák

Zelles

et al. 2010

The Anatomical Record

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“…Furthermore, since variations in the total power of the EEG signal were related to behavioral modifications, occurrence of tremor, and partial seizures, these can be considered as an appropriate surrogate PD endpoint for the investigation of the epileptogenic activity of antibiotics in rats. Compared to EEG recording used in previously published studies, 29,30 the integrated PK-PD modeling approach used here constituted a major improvement. Because GEM is supposed to interact with GABAa receptor 43 an indirect response model with inhibition of the factors controlling drug response (i.e., inhibition of GABAa binding to its receptor sites) was initially Figure 5.…”

Section: Discussionmentioning

confidence: 97%

“…This approach had occasionally been used to assess the epileptogenic effects of drugs, including antibiotics, [29][30][31] and could be considerably improved by coupling quantitative EEG recording with PK-PD modeling analysis, as previously done to investigate the desirable CNS effects of drugs. 32,33 We have investigated the convulsant activity of gemifloxacin (GEM) by above-mentioned crude PK-PD approaches in laboratory animals.…”

Section: Introductionmentioning

confidence: 99%

Retracted: Convulsant activity and pharmacokinetic–pharmacodynamic modeling of the electroencephalogram effect of gemifloxacin in rats

Roy

Bose

Bhaumik

et al. 2010

Journal of Pharmaceutical Sciences

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“…Furthermore, since variations in the total power of the EEG signal were related to behavioral modifications and occurrence of tremor and partial seizures, changes in EEG can be considered as an appropriate surrogate pharmacodynamic endpoint for the investigation of the epileptogenic activity of imipenem in rats. Compared to EEG recording used in previously published studies (14,16), the integrated PK-PD modeling approach used here constituted a major improvement. Because imipenem is supposed to interact with GABA A receptors (8,16), an indirect-response model with inhibition of the factors controlling drug response (that is, inhibition of GABA A binding to its receptor sites) was initially selected but was unable to capture the lag time followed by a sudden increase in the EEG effect (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…This approach had occasionally been used to assess the epileptogenic effects of drugs, including antibiotics (14,16,17), and could be considerably improved by coupling quantitative EEG recording with PK-PD modeling analysis, as previously done to investigate the desirable CNS effects of drugs (6,26).…”

mentioning

confidence: 99%

Pharmacokinetic-Pharmacodynamic Modeling of the Electroencephalogram Effect of Imipenem in Healthy Rats

Dupuis¹,

Couet²,

Paquereau³

et al. 2001

Antimicrob Agents Chemother

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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. Indirecteffect 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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Effects of some quinolones on imipenem-induced seizures in DBA/2 mice

Cited by 21 publications

References 41 publications

Modification of Innervation Pattern by Fluoroquinolone Treatment in the Rat Salivary Glands

Modification of Innervation Pattern by Fluoroquinolone Treatment in the Rat Salivary Glands

Retracted: Convulsant activity and pharmacokinetic–pharmacodynamic modeling of the electroencephalogram effect of gemifloxacin in rats

Pharmacokinetic-Pharmacodynamic Modeling of the Electroencephalogram Effect of Imipenem in Healthy Rats

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