Effects of fluoroquinolone antimicrobials alone and in conjunction with theophylline on seizures in amygdaloid kindled rats. Mechanistic and pharmacokinetic study.
The influence of three fluoroquinolone (FQ) antimicrobial drugs (ciprofloxacin (CP), norfloxacin (NF), enrofloxacin (EF)) on seizure parameters in amygdaloid kindled rats was investigated. CP and NF (100 mg/kg i.p.) did not modify seizure parameters while EF induced a decrease in seizure activity. Since clinical data indicate a seizure enhancing interaction between FQ and theophylline (THEO) we studied the influence of concurrent FQ-THEO administration in kindled rats. CP and NF, but not EF given concurrently with a non-seizure modulating dose of THEO (10 mg/kg i.p.) caused increases in seizure activity and aggressiveness in the animals. The CP-THEO induced seizure enhancement was antagonized by 2-chloroadenosine and diazepam. Pharmacokinetic studies demonstrated that THEO serum levels and elimination were not altered by concurrent CP administration. We conclude that coadministration of FQ-THEO can aggravate amygdala kindled seizures and that this aggravation may involve centrally mediated mechanisms.
Vancutsem
P M
PM
Department of Pharmacology, NYSCVM, Cornell University, Ithaca 14853-6401.
Schwark
W S
WS
D015762:2-Chloroadenosine / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects*; D000818:Animals; D000890:Anti-Infective Agents / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004567:Electrodes, Implanted; D000077422:Enrofloxacin; D005260:Female; D024841:Fluoroquinolones; D007696:Kindling, Neurologic / Q000187:drug effects*; D009643:Norfloxacin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015363:Quinolones / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology; D013806:Theophylline / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; D015762:2-Chloroadenosine; D000077422:Enrofloxacin; D013806:Theophylline; D009643:Norfloxacin; D003975:Diazepam