title: Effects of fluoroquinolone antimicrobials alone and in conjunction with theophylline on seizures in amygdaloid kindled rats. Mechanistic and pharmacokinetic study.
abstract: 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.
authors.affiliation: Department of Pharmacology, NYSCVM, Cornell University, Ithaca 14853-6401.
authors.forename: P M
authors.initials: PM
authors.lastname: Vancutsem
authors.forename: W S
authors.initials: WS
authors.lastname: Schwark
mesh_terms: 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*
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; D015762:2-Chloroadenosine; D000077422:Enrofloxacin; D013806:Theophylline; D009643:Norfloxacin; D003975:Diazepam