Quantitative comparison of the convulsive activity of combinations of twelve fluoroquinolones with five nonsteroidal antiinflammatory agents

Jahye Kim, Hisakazu Ohtani, Masayuki Tsujimoto, Yasufumi Sawada

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Concomitant administration of certain fluoroquinolone antimicrobials and nonsteroidal antiinflammatory agents (NSAIDs) induces serious convulsion in humans. There are differences in convulsive activity among fluoroquinolones and in the potentiation of fluoroquinolone-induced convulsion among NSAIDs, but a comprehensive, quantitative comparison has not been carried out. This study evaluates the inhibitory effects of twelve fluoroquinolones (ciprofloxacin, enoxacin, fleroxacin, gatifloxacin, levofloxacin, lomefloxacin, norfloxacin, ofloxacin, pazufloxacin, prulifloxacin, sparfloxacin, and tosufloxacin) alone or in the presence of an NSAID (4-biphenylacetic acid, diclofenac sodium, loxoprofen, lornoxicam or zaltoprofen) on the GABAA receptor binding of [3H]muscimol in an in vitro study using mice synaptic plasma membrane. The rank order of inhibitory effects of the fluoroquinolones was prulifloxacin≈norfloxacin> ciprofloxacin≥enoxacin>gatifloxacin≥ ofloxacin≈tosufloxacin≈lomefloxacin> levofloxacin≥sparfloxacin≥ pazufloxacin≈fleroxacin. 4-Biphenylacetic acid most potently enhanced the inhibitory effects of the fluoroquinolones, while zaltoprofen, loxoprofen, lornoxicam and diclofenac had essentially no effect. The clinical risk of convulsion for each combination was estimated using a pharmacodynamic model based on receptor occupancy using the in vitro data set obtained and pharmacokinetic parameters in humans collected from the literature. The combinations of 4-biphenylacetic acid with prulifloxacin and enoxacin were concluded to be the most hazardous.

Original languageEnglish
Pages (from-to)167-174
Number of pages8
JournalDrug Metabolism And Pharmacokinetics
Volume24
Issue number2
DOIs
Publication statusPublished - 2009 Jan 1
Externally publishedYes

Keywords

  • Drug interaction
  • Fluoroquinolone
  • GABA inhibition
  • NSAIDs
  • Pharmacodynamic modeling

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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