Single-dose pharmacokinetics and genotoxicity of metronidazole in cats.
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.
Sekis
Ivana
I
Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Tower Road, Ithaca, NY 14853, United States.
Ramstead
Kerry
K
Rishniw
Mark
M
Schwark
Wayne S
WS
McDonough
Sean P
SP
Goldstein
Richard E
RE
Papich
Mark
M
Simpson
Kenneth W
KW
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D002371:Cat Diseases / Q000188:drug therapy; D002415:Cats / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D020552:Comet Assay / Q000662:veterinary; D004247:DNA / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007262:Infusions, Intravenous / Q000662:veterinary; D005256:Leukemia Virus, Feline / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008795:Metronidazole / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity*; D009152:Mutagenicity Tests / Q000662:veterinary
D000890:Anti-Infective Agents; D008795:Metronidazole; D004247:DNA