Pharmacokinetics of medetomidine and atipamezole in dairy calves: an agonist-antagonist interaction

Medetomidine and atipamezole are licensed for use in dogs and cats in sever al countries and are highly selective and specific alpha(2)-adrenoceptor ag ents. The pharmacokinetics of the agonist medetomidine and the antagonist a tipamezole were studied in a cross-over trial in eight dairy calves, The an imals were injected intravenously (i.v.) with medetomidine (40 mu g/kg i.v. ), followed by atipamezole (200 mu g/kg i.v,) or saline after 60 min, The w ash-out period between experiments was 1 week, Drug concentrations in plasm a were determined using HPLC. Atipamezole significantly (P < 0.05) increase d the AUMC and MRT of medetomidine due to an increase in the medetomidine c oncentration when atipamezole was injected i.v, The mean increment in medet omidine concentration was 6.4 ng/mL, increased levels having a mean duratio n of 39.4 min. Other pharmacokinetic parameters of medetomidine were not si gnificantly altered by atipamezole. Sedative effects of the agonist, and th e effectiveness of the antagonist were recorded. All the animals relapsed i nto sedation on average 80 min after reversal with atipamezole, It is likel y that the increase in medetomidine concentration after the injection of at ipamezole i.v, results from displacement of medetomidine from alpha(2)-adre noceptors in highly perfused tissues.