Effects of fluoroquinolones on the locomotor activity in rats.
During therapy with fluoroquinolones adverse CNS reactions such as dizziness, light-headedness, insomnia or sleepiness are observed in up to 20% of patients. Using a device developed at our institute for the simultaneous registration of the activity of rats housed in single cages, we have investigated the effects of trovafloxacin, fleroxacin or ofloxacin on the locomotor activity of juvenile and adult rats (11 per group) after oral administration of 600 mg/kg for 5 consecutive days. The effects were most pronounced after fleroxacin, which induced a reduction in activity to 36 +/- 9% (mean +/- SD) of the values measured in juvenile rats before treatment and to 60 +/- 21% (mean +/- SD) in adult rats. HPLC analysis of the plasma concentrations in juvenile rats showed that the concentrations of trovafloxacin were considerably lower than those of the other fluoroquinolones that had been studied previously in our laboratory: the peak concentration of trovafloxacin was 14 +/- 2.9 mg/l (mean +/- SD) after a single dose of 600 mg/kg in juvenile rats. Overall, we showed that the locomotor activities of juvenile and adult rats were significantly depressed during treatment with fluoroquinolones. The effects were more pronounced in juveniles. Monitoring of the locomotor activity of rats is a suitable approach to study CNS effects of fluoroquinolones in animals, but pharmacokinetics have to be taken into account.
Thiel
R
R
Institute of Clinical Pharmacology and Toxicology, Department of Toxicology, Benjamin Franklin Medical Center, Freie Universität Berlin, Garystrasse 5, 14195 Berlin, Germany. rthiel@zedat.fu-berlin.de
Metzner
S
S
Gericke
C
C
Rahm
U
U
Stahlmann
R
R
D000284:Administration, Oral; D000367:Age Factors; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D016576:Fleroxacin / Q000494:pharmacology; D024841:Fluoroquinolones; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D009287:Naphthyridines / Q000097:blood / Q000494:pharmacology; D015242:Ofloxacin / Q000494:pharmacology; D010775:Photic Stimulation; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000890:Anti-Infective Agents; D004791:Enzyme Inhibitors; D024841:Fluoroquinolones; D009287:Naphthyridines; C080163:trovafloxacin; D015242:Ofloxacin; D016576:Fleroxacin