Single-dose pharmacokinetics and genotoxicity of metronidazole in cats

J Feline Med Surg. 2009 Feb;11(2):60-8. doi: 10.1016/j.jfms.2008.06.011. Epub 2009 Jan 19.

Abstract

Single-dose pharmacokinetics and genotoxicity of metronidazole in cats were evaluated. Cats received either 5mg/kg metronidazole intravenously, or 20mg/kg metronidazole benzoate (12.4mg/kg metronidazole base) orally in a single dose. Serial plasma samples were collected and assayed for metronidazole using high pressure liquid chromatography (HPLC). Genotoxicity was assessed in vitro in feline peripheral blood mononuclear cells (PBMC) and a feline T-cell lymphoma line incubated with metronidazole, and in vivo in PBMC collected before, during and 7 days after oral metronidazole, by use of the COMET assay. Systemic absorption of metronidazole was variable (mean=65+/-28%) with a peak of 8.84+/-5.4microg/ml at 3.6+/-2.9h. The terminal half-life was 5.34h from the intravenous dose and 5.16h from the oral dose. Systemic clearance was low (mean=91.57ml/h/kg [1.53ml/kg/min]), and the apparent volume of distribution (steady state) was 0.650+/-0.254l/kg. Genotoxicity was detected at all concentrations of metronidazole in feline PBMC and the T-cell lymphoma line in vitro. Genotoxicity was also observed in PBMC collected from cats after 7 days of oral metronidazole but resolved within 6 days of discontinuing metronidazole.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Analysis of Variance
  • Animals
  • Anti-Infective Agents / blood
  • Anti-Infective Agents / pharmacokinetics*
  • Anti-Infective Agents / toxicity*
  • Cat Diseases / drug therapy
  • Cats / blood
  • Cats / genetics*
  • Cats / metabolism*
  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid / veterinary
  • Comet Assay / veterinary
  • DNA / drug effects
  • Dose-Response Relationship, Drug
  • Infusions, Intravenous / veterinary
  • Leukemia Virus, Feline / drug effects
  • Leukocytes, Mononuclear / drug effects
  • Metronidazole / blood
  • Metronidazole / pharmacokinetics*
  • Metronidazole / toxicity*
  • Mutagenicity Tests / veterinary

Substances

  • Anti-Infective Agents
  • Metronidazole
  • DNA