Determination of the inhibitory potential of 6 fluoroquinolones on CYP1A2 and CYP2C9 in human liver microsomes

Acta Pharmacol Sin. 2008 Dec;29(12):1507-14. doi: 10.1111/j.1745-7254.2008.00908.x.


Aim: To determine the inhibitory potential of 2 new fluoroquinolones, caderofloxacin and antofloxacin, together with 4 marketed fluoroquinolones, moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin, on the activity of cytochrome P450 isoforms 1A2 (CYP1A2) and 2C9 (CYP2C9).

Methods: Probe substrates, phenacetin (CYP1A2), and tolbutamide (CYP2C9) were incubated with human liver microsomes and the metabolites were analyzed by liquid chromatography/mass spectrometry using electrospray ionization in positive or negative mode. Glipizide was used as the internal standard in both modes. The inhibitory potential of fluoroquinolones on CYP1A2 and CYP2C9 was investigated.

Results: The IC50 values (micromol/L) determined with the cocktail were in agreement with individual probe substrates (alpha-naphthoflavone: 0.27 vs 0.26; sulfaphenazole: 0.49 vs 0.37). Ciprofloxacin showed weak inhibition on both the activity of CYP1A2 (IC50 135 micromol/L) and CYP2C9 (IC50 180 micromol/L), whereas levofloxacin inhibited only CYP2C9 (IC50 210 micromol/L). Caderofloxacin, antofloxacin, moxifloxacin, and gatifloxacin showed little or no inhibition on the activity of CYP1A2 or CYP2C9 when tested at comparable concentrations (0-200 mg/L).

Conclusion: Caderofloxacin, antofloxacin, moxifloxacin, and gatifloxacin are negligible inhibitors to CYP1A2 and CYP2C9. The in vitro system can be used as a high-throughput model to screen similar compounds for the early identification of drug-drug interaction potential.

MeSH terms

  • Animals
  • Anti-Infective Agents / pharmacology*
  • Aryl Hydrocarbon Hydroxylases / antagonists & inhibitors*
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Aza Compounds / pharmacology
  • Ciprofloxacin / pharmacology
  • Cytochrome P-450 CYP1A2 / metabolism
  • Cytochrome P-450 CYP1A2 Inhibitors*
  • Cytochrome P-450 CYP2C9
  • Fluoroquinolones / pharmacology*
  • Gatifloxacin
  • Humans
  • Isoenzymes / antagonists & inhibitors*
  • Isoenzymes / metabolism
  • Levofloxacin
  • Microsomes, Liver* / drug effects
  • Microsomes, Liver* / enzymology
  • Molecular Structure
  • Moxifloxacin
  • Ofloxacin / analogs & derivatives
  • Ofloxacin / pharmacology
  • Quinolines / pharmacology
  • Reproducibility of Results


  • Anti-Infective Agents
  • Aza Compounds
  • Cytochrome P-450 CYP1A2 Inhibitors
  • Fluoroquinolones
  • Isoenzymes
  • Quinolines
  • cadrofloxacin
  • antofloxacin
  • Ciprofloxacin
  • Levofloxacin
  • Ofloxacin
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP1A2
  • Gatifloxacin
  • Moxifloxacin