title: The pharmacokinetics of diminazene aceturate after intramuscular administration in healthy dogs.
abstract: The pharmacokinetics of diminazene aceturate following intramuscular (i.m.) administration at 4.2 mg/kg was evaluated in 8 healthy German Shepherd dogs. Blood samples were collected at 19 intervals over a period of 21 days. Diminazene plasma concentrations were measured using a validated HPLC method with UV detection and a sensitivity of 25 ng/ml. The in vitro and in vivo binding of diminazene to blood elements was additionally determined. Diminazene pharmacokinetics showed a large inter-individual variation after i.m. administration. It had a short absorption half-life (K01-HL of 0.11 +/- 0.18 h), resulting in a C(max) of 1849 +/- 268.7 ng/ml at T(max) of 0.37 h and a mean overall elimination half-life (T1/2beta) of 5.31 +/- 3.89 h. A terminal half-life of 27.5 +/- 25.0 h was measured. At 1 h after i.m. injection, 75% of the diminazene in whole blood was in the plasma fraction. The results of this study indicate that diminazene is rapidly distributed and sequestered into the liver, followed by a slower terminal phase during which diminazene is both redistributed to the peripheral tissues and/or renally excreted. It is recommended that diminazene administered i.m. at 4.2 mg/kg should not be repeated within a 21-day period.
authors.affiliation: Department of Companion Animal Studies, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, Onderstepoort 0110, South Africa.
authors.forename: D M
authors.initials: DM
authors.lastname: Miller
authors.forename: G E
authors.initials: GE
authors.lastname: Swan
authors.forename: R G
authors.initials: RG
authors.lastname: Lobetti
authors.forename: L S
authors.initials: LS
authors.lastname: Jacobson
mesh_terms: D000042:Absorption; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000662:veterinary; D004133:Diminazene / Q000097:blood / Q000493:pharmacokinetics*; D004285:Dogs / Q000378:metabolism*; D006207:Half-Life; D007273:Injections, Intramuscular / Q000662:veterinary; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D014018:Tissue Distribution; D014344:Trypanocidal Agents / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D014344:Trypanocidal Agents; D004133:Diminazene