Pharmacokinetics of moxifloxacin in non-inflamed cerebrospinal fluid of humans: implication for a bactericidal effect.
OBJECTIVE
To evaluate the ability of moxifloxacin to penetrate healthy brain barriers.


METHODS
Fifty patients received a single oral dose of 400 mg as an antimicrobial prophylaxis regimen for a short urological procedure under spinal anaesthesia. Serum and cerebrospinal fluid (CSF) were sampled at different time intervals post-drug intake and patients were divided into five groups, as follows: group I: 0.5-1 h; group II: 1-2 h; group III: 2-4 h; group IV: 4-6 h; and group V: 6-8 h. Concentrations of moxifloxacin were estimated after analysis by an HPLC system. Bactericidal activity of CSF samples of groups III and IV was assessed by a microdilution technique against two penicillin-resistant isolates of Streptococcus pneumoniae with MICs of moxifloxacin of 0.19 and 0.125 mg/L, respectively.


RESULTS
Mean CSF concentrations of moxifloxacin of groups I, II, III, IV and V were 0.19, 0.87, 3.00, 4.07 and 1.82 mg/L, respectively. The mean bactericidal activity of CSF of group III was 8 and that of group IV was 4.


CONCLUSIONS
Single oral intake of 400 mg moxifloxacin is accompanied by good penetration through healthy meninges within 2-6 h post-dose and reached adequately high levels in human CSF exerting satisfactory bactericidal activity against penicillin-resistant S. pneumoniae. These results render novel perspectives for a role of moxifloxacin in CNS infections.
Kanellakopoulou
Kyriaki
K
4th Department of Internal Medicine, University of Athens, Medical School, Athens, Greece. kyrkanel@yahoo.gr
Pagoulatou
Alexandra
A
Stroumpoulis
Konstantinos
K
Vafiadou
Marianthi
M
Kranidioti
Hariklia
H
Giamarellou
Helen
H
Giamarellos-Bourboulis
Evangelos J
EJ
D000368:Aged; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D001372:Aza Compounds / Q000493:pharmacokinetics* / Q000494:pharmacology; D002555:Cerebrospinal Fluid / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D024841:Fluoroquinolones; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D008875:Middle Aged; D000077266:Moxifloxacin; D011804:Quinolines / Q000493:pharmacokinetics* / Q000494:pharmacology; D044967:Serum / Q000737:chemistry; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013997:Time Factors
D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin