title: Cerebrospinal fluid transport and disposition of the quinolones ciprofloxacin and pefloxacin in rats.
abstract: The disposition of ciprofloxacin and pefloxacin in the rat cerebrospinal fluid (CSF) was investigated after i.v. and i.c.v. administration. After injection into the lateral ventricle, the terminal half-life of pefloxacin was shorter than that of ciprofloxacin. After i.v. infusions, the relative CSF exposure, expressed as CSF: area under the plasma concentration time curve ratio, were found to be 10.4 +/- 2.8% for ciprofloxacin and 42.4 +/- 3.0% for pefloxacin. The unit impulse response methodology was applied in order to assess the CSF transport profile. The plasma-CSF transport clearance of pefloxacin and the total amount of drug transported into the CSF were significantly higher compared with ciprofloxacin. Although pefloxacin exhibited a linear CSF transport profile, the plasma-CSF transport clearance of ciprofloxacin was found to be nonlinear at the dose level studied. Pefloxacin was converted in the brain to the active metabolite norfloxacin (N-desmethyl pefloxacin). The difference in CSF exposure of both quinolones and the presence of active metabolites of N-methylated quinolones in the CSF may be of clinical relevance in the treatment of CNS infections, but differences in antimicrobial activity have to be taken into account as well.
authors: Center for Bio-Pharmaceutical Sciences, Leiden University, The Netherlands.
authors: U
authors: U
authors: Jaehde
authors: M W
authors: MW
authors: Langemeijer
authors: A G
authors: AG
authors: de Boer
authors: D D
authors: DD
authors: Breimer
mesh_terms: D000818:Animals; D001692:Biological Transport; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000134:cerebrospinal fluid*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D015366:Pefloxacin / Q000008:administration & dosage / Q000134:cerebrospinal fluid*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility
chemical_list: D015366:Pefloxacin; D002939:Ciprofloxacin