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Abstract

Cerebrospinal fluid transport and disposition of the quinolones ciprofloxacin and pefloxacin in rats.

U Jaehde, M W Langemeijer, A G de Boer and D D Breimer
Journal of Pharmacology and Experimental Therapeutics December 1992, 263 (3) 1140-1146;
U Jaehde
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M W Langemeijer
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A G de Boer
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D D Breimer
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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.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 263, Issue 3
1 Dec 1992
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Abstract

Cerebrospinal fluid transport and disposition of the quinolones ciprofloxacin and pefloxacin in rats.

U Jaehde, M W Langemeijer, A G de Boer and D D Breimer
Journal of Pharmacology and Experimental Therapeutics December 1, 1992, 263 (3) 1140-1146;

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Abstract

Cerebrospinal fluid transport and disposition of the quinolones ciprofloxacin and pefloxacin in rats.

U Jaehde, M W Langemeijer, A G de Boer and D D Breimer
Journal of Pharmacology and Experimental Therapeutics December 1, 1992, 263 (3) 1140-1146;
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