@article {Jaehde1140, author = {U Jaehde and M W Langemeijer and A G de Boer and D D Breimer}, title = {Cerebrospinal fluid transport and disposition of the quinolones ciprofloxacin and pefloxacin in rats.}, volume = {263}, number = {3}, pages = {1140--1146}, year = {1992}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, 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.}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/263/3/1140}, eprint = {https://jpet.aspetjournals.org/content/263/3/1140.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }