Document Detail

Convulsant activity and pharmacokinetic-pharmacodynamic modeling of the electroencephalogram effect of gemifloxacin in rats.
MedLine Citation:
PMID:  19670296     Owner:  NLM     Status:  MEDLINE    
A pharmacokinetic-pharmacodynamic (PK-PD) modeling approach was used to investigate the epileptogenic activity of gemifloxacin as a representative antibiotic with concentration-dependent antimicrobial activity. Rats received an intravenous infusion of gemifloxacin at a rate of 4 mg kg of body weight(-1) min(-1) over 50 min. Blood samples were collected for drug assay, and an electroencephalogram (EEG) was recorded during infusion and postinfusion. An important delay was observed between concentrations of gemifloxacin in plasma 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 by using an effect compartment model with a spline function to describe the relationship between effect and concentration at the effect site. The robustness of the PK-PD model was then assessed by keeping the dose constant but increasing the duration of infusion to 100 and 200 min. Although this was accompanied by PK modifications, PD parameters did not vary significantly, and the PK-PD model still applied. In conclusion, the successful PK-PD modeling of the gemifloxacin EEG effect in rats should be considered to predict and reduce the epileptogenic risk associated with this antibiotic as a representative fluoroquinolone.
Bikash Roy; Anirbandeep Bose; Uttam Bhaumik; Ayan Das; Nilendra Chatterjee; Animesh Ghosh; Soumendra Darbar; Amlan Kanti Sarkar; Pinaki Sengupta; T K Pal
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Publication Detail:
Type:  Journal Article; Retracted Publication    
Journal Detail:
Title:  Journal of pharmaceutical sciences     Volume:  99     ISSN:  1520-6017     ISO Abbreviation:  J Pharm Sci     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-01-19     Completed Date:  2010-04-02     Revised Date:  2012-02-13    
Medline Journal Info:
Nlm Unique ID:  2985195R     Medline TA:  J Pharm Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1535-47     Citation Subset:  IM    
Copyright Information:
2009 Wiley-Liss, Inc. and the American Pharmacists Association
Department of Pharmaceutical Technology, Bioequivalence Study Centre, Jadavpur University, Kolkata 700 032, India.
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MeSH Terms
Anti-Bacterial Agents / adverse effects*,  pharmacokinetics*
Dose-Response Relationship, Drug
Electroencephalography / drug effects*
Fluoroquinolones / adverse effects*,  pharmacokinetics*
Models, Statistical
Naphthyridines / adverse effects*,  pharmacokinetics*
Rats, Wistar
Seizures / chemically induced*
Time Factors
Tremor / chemically induced
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Fluoroquinolones; 0/Naphthyridines; 175463-14-6/gemifloxacin
Retraction In:
J Pharm Sci. 2012 Feb;101(2):885   [PMID:  22319775 ]

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