摘要：

The pharmacokinetics of detomidine, a novel analgesic sedative, was studied in the major target species after high (80 μg/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 Vkg, cow 1.89 l/kg) than after i.v. dosing (horse 0.74 l/kg, cow 0.73 Vkg). 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, im.) 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. Jktomidine did not accumulate in tissues. All tissue concentrations measured 48 h after dosing were less than 3% of the original dose per weight unit. Both magnitude and duration of the drug's action closely paralleled its serum pharmacokinetics. In this respect no difference between equine and bovine species was observed.

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