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  • Title: Neurotoxicity and toxicokinetics of norfloxacin in conscious rats.
    Author: Zhang LR, Wang YM, Chen BY, Cheng NN.
    Journal: Acta Pharmacol Sin; 2003 Jun; 24(6):605-9. PubMed ID: 12791190.
    Abstract:
    AIM: To study the neurotoxicity and toxicokinetics of norfloxacin (NFLX) in freely moving rats. METHODS: Rats were assigned randomly to four treatment groups that received a single iv dose of 50, 100, 200 mg/kg of NFLX and 0.9 % saline, respectively. Electroencephalogram (EEG) was continuously recorded with a computerized system in freely moving rats. Venous blood samples were collected for determination of the NFLX concentration by microbioassay method with Escherichia coli 441102 as the test strain. Toxicokinetic parameters were determined from serum concentration-time data with the 3p97 program. RESULTS: (1) The epileptiform discharges appeared in all NFLX groups with different latent periods, accompanied with limb twitching and clonic-tonic seizures. The relative total power of the EEG increased. (2) Drug serum concentration-time curves of different doses conformed to a two-compartmental model. The values of clearance, volume of distribution, and terminal half-life were dose-independent, while maximum serum concentrations (Cmax) and the areas under the concentration-time curve (AUC(0-infinity)) of NFLX increased with dosage. (3) The relative total powers of EEG were closely correlated with the administered dose, Cmax as well as AUC(0-infinity). CONCLUSION: The present study established a suitable approach to quantitatively determine central nervous system (CNS) stimulant effect of NFLX. There is a significant correlation between AUC(0-infinity) and the changes of relative total power, which may serve as the index for judgement and prediction of the CNS toxic effect induced by NFLX.
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