The pharmacokinetics of diminazene aceturate after intramuscular administration in healthy dogs

Abstract

The pharmacokinetics of din-dnazene 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 din-dnazene 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 Cmax of 1849 ± 268.7 ng/mlat Tr.,, of 0.37 h and a mean overall elimination half-life (T1/2β) 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 dirazene administered i.m. at 4.2 mg/kg should not be repeated within a 21-day period.