Pharmacokinetics of diminazene in sheep.
The pharmacokinetic behavior of diminazene in plasma after administration of 2 mg/kg i.v. and 3.5 mg/kg i.m. was studied in four healthy Dala x Ryggja rams. Following i.v. injection, the data were satisfactorily described by a tri-exponential equation; the apparent volume of distribution at the steady-state was 0.56 +/- 0.04 L/Kg (mean +/- SD; n = 4); total body clearance averaged 1.1 +/- 0.09 ml/kg/min and elimination half-life was 9.30 +/- 1.40 hr. After intramuscular administration peak plasma levels of 6.30-7.57 micrograms/ml were reached in 20 to 45 min and the mean absorption time averaged 5.83 +/- 1.61 hr. Systemic availability relative to the intravenous dose was 95.10 +/- 23.21% and mean residence time averaged 14.16 +/- 1.55 hr. The partition of diminazene between erythrocytes and plasma averaged 0.64 +/- 0.10; plasma protein binding was high (65-85%) and concentration-dependent. Based on the experimental data obtained, an initial i.m. dose of 2.5 mg/kg followed by 2 mg/kg 24 hr later should be safe and effective in cases of babesiosis and trypanosomiasis sensitive to diminazene. A preslaughter withdrawal period of 14-26 days was estimated.
D000578:Amidines / Q000378:metabolism*; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D004133:Diminazene / Q000008:administration & dosage / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism; D006207:Half-Life; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D010950:Plasma Cells / Q000378:metabolism; D011485:Protein Binding; D012756:Sheep; D013997:Time Factors; D014018:Tissue Distribution
D000578:Amidines; D001798:Blood Proteins; D004133:Diminazene