Single-dose pharmacokinetics and genotoxicity of metronidazole in cats

Journal of Feline Medicine and Surgery - Tập 11 - Trang 60-68 - 2009
Ivana Sekis1, Kerry Ramstead1, Mark Rishniw1, Wayne S. Schwark2, Sean P. McDonough3, Richard E. Goldstein1, Mark Papich4, Kenneth W. Simpson1
1Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Tower Road, Ithaca, NY 14853, United States
2Department of Molecular Medicine, Cornell University, Tower Road, Ithaca, NY 14853, United States
3Department of Biomedical Sciences, Cornell University, Tower Road, Ithaca, NY 14853, United States
4College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, United States

Tóm tắt

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.

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Thông tin
Thông tin xuất bản

Journal of Feline Medicine and Surgery

Tập 11

60-68

Thông tin tác giả