Single-dose pharmacokinetics of detomidine in the horse and cow.
The pharmacokinetics of detomidine, a novel analgesic sedative, was studied in the major target species after high (80 micrograms/kg) i.v. and i.m. doses. In addition, drug residues in some organs were determined. Concentrations were measured using a sensitive, detomidine-specific radio-immunoassay method. Rapid absorption following i.m. dosing occurred. Absorption half-lives were 0.15 h (horse) and 0.08 h (cattle). The mean peak concentration in the horse (51.3 ng/ml) was achieved in 0.5 h and in the cow (65.8 ng/ml) in 0.26 h. The areas under the concentration curve after i.m. dosing were 66% (horse) and 85% (cow) of the corresponding i.v. values. Distribution was rapid with half-lives of 0.15 h (horse, i.v.) and 0.24 h (cow, i.v.). The apparent volume of distribution was higher after the i.m. dosing (horse 1.56 l/kg, cow 1.89 l/kg) than after i.v. dosing (horse 0.74 l/kg, cow 0.73 l/kg). Elimination half-lives were 1.19 h (horse) and 1.32 h (cow) for the i.v. dose and 1.78 h (horse) and 2.56 h (cow) for the i.m. dose. Total clearances ranged from 6.7 (horse, i.v.) to 12.3 (cow, i.m.) ml/min/kg. Renal clearances were less than 1% of the total clearances showing negligible excretion of the drug in urine and suggesting elimination by metabolism. A cross-reacting metabolite in urine corresponded to less than 1.5% of the detomidine dose's immunoreactivity. High-dose detomidine increased urine flow significantly. Excretion of detomidine in milk in cattle was extremely low. No detectable amounts were present 23 h after dosing.(ABSTRACT TRUNCATED AT 250 WORDS)
Salonen
J S
JS
Farmos Group Ltd., Research Center, Turku, Finland.
Vähä-Vahe
T
T
Vainio
O
O
Vakkuri
O
O
D000042:Absorption; D000700:Analgesics / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D000818:Animals; D002417:Cattle / Q000378:metabolism*; D004350:Drug Residues / Q000032:analysis; D005260:Female; D006207:Half-Life; D006736:Horses / Q000378:metabolism*; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D007093:Imidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D007273:Injections, Intramuscular / Q000662:veterinary; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D008892:Milk / Q000378:metabolism; D014018:Tissue Distribution
D000700:Analgesics; D006993:Hypnotics and Sedatives; D007093:Imidazoles; C041255:detomidine