Single-dose pharmacokinetics and genotoxicity of metronidazole in cats

Abstract

Single-dose pharmacokinetics and genotoxicity of metronidazole in cats were evaluated. Cats received either 5 mg/kg metronidazole intravenously, or 20 mg/kg metronidazole benzoate (12.4 mg/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±5.4 μg/ml at 3.6±2.9 h. The terminal half-life was 5.34 h from the intravenous dose and 5.16 h from the oral dose. Systemic clearance was low (mean=91.57 ml/h/kg [1.53 ml/kg/min]), and the apparent volume of distribution (steady state) was 0.650±0.254 l/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.