PENETRATION OF FLUOROQUINOLONES INTO HUMAN CEREBROSPINAL FLUID
1990 Volume 38 Issue 5 Pages 461-476
Details
1990 Volume 38 Issue 5 Pages 461-476
To clarify the relationship between CNS toxicity and penetration of fluoroquinolones into human cerebrospinal fluid (CSF), five agents, namely, norfloxacin (NFLX), enoxacin (ENX), ofloxacin (OFLX), ciprofloxacin (CPFX) and fleroxacin (AM-833) were given preoperatively to 193 patients with urological diseases. CSF and blood samples were collected during spinal anesthesia at surgery.
1) Firstly, a single dose of 200 mg of drug was given to patients 3 h before lumbar anesthesia. The mean CSF concentration (mean±SE) of AM-833 (0.412±0.082μg/ml) was the highest, followed by OFLX, ENX, CPFX, and NFLX. There were statistically significant differences among AM-833, OFLX>ENX**>CPFX, NFLX**p<0.01, DUNCAN'S multiple comparison procedures) The CSF/serum concentration ratio showed essentially the same tendency.
2) NFLX, ENX or OFLX was given in consecutive doses of 600 mg /day, t. i. d. for 3 days, or CPFX at 600 mg/day, t.i.d. for 5 days, or AM-833 at 200 mg /day once a day for 3 days. CSF samples were collected 3 h after the last dose. In the consecutive dose group, CSF concentrations and CSF/serum ratios were as follows: ENX**(0.661±0.085μg/ml, 0.289±0.028), OFLX**(0.935 ± 0.156μg/ml, 0.315±0.032), CPFX**(0.128±0.014μg/ml, 0.125±0.011) and AM-833*(0.898±0.136μg/ml, 0.304±0.122)*p<0.05, **p<0.01, STUDENT'S t-test). Thus, higher CSF levels and CSF/serum ratios were demonstrated in the consecutive dose group.
3) In the single-dose group of 300 mg of AM-833, the CSF concentration was 0.599± 0.134 μg/ml and the CSF/serum ratio 0.198±0.228. In the consecutive dose group, these values were 1.292±0.154μg/ml and 0.323±0.217. These data suggest dose-dependency for fluoroquinolones.
4) A pharmacokinetic analysis was performed in 28 patients given OFLX and in 25 given AM-833. Plasma and CSF concentration-time profiles of these agents were fitted to a one-compartment open model. The half-life in plasma was 3.9 h for OFLX and 9.0 h for AM-833. CSF levels peaked at 6 h for OFLX and 7 h for AM-833, and subsequently decreased gradually.
These findings suggest that fluoroquinolones penetrated into CSF in patients who had never suffered from cerebrospinal disease.
