Single-dose pharmacokinetics and genotoxicity of metronidazole in cats

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). Gen toxicity 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 mu g/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. (C) 2008 ESFM and AAFP. Published by Elsevier Ltd. All rights reserved.