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  • Title: A pharmacokinetic study including some relevant clinical effect of medetomidine and atipamezole in lactating dairy cows.
    Author: Ranheim B, Arnemo JM, Ryeng KA, Søli NE, Horsberg TE.
    Journal: J Vet Pharmacol Ther; 1999 Dec; 22(6):368-73. PubMed ID: 10651465.
    Abstract:
    Medetomidine is the most potent and selective alpha2-agonist used in veterinary medicine and its effects can be antagonized by the alpha2-antagonist atipamezole. The pharmacokinetics of medetomidine and atipamezole were studied in a cross-over trial in eight lactating dairy cows. The animals were injected intravenously (i.v.) with medetomidine (40 microg/kg) followed by atipamezole i.v. (200 microg/kg) or saline i.v. after 60 min. Drug concentrations in plasma were measured by HPLC. After the injection of atipamezole, the concentration of medetomidine in plasma increased slightly, the mean increment being 2.7 ng/mL and the mean duration 12.1 min. However, atipamezole did not alter the pharmacokinetics of medetomidine. It is likely that the increase in medetomidine concentration is caused by displacement of medetomidine by atipamezole in highly perfused tissues. The volume of distribution at steady state (Vss) for medetomidine followed by saline and medetomidine followed by atipamezole was 1.21 and 1.32 L/kg, respectively, whereas the total clearance (Cl) values were 24.2 and 25.8 mL/min x kg. Vss and Cl values for atipamezole were 1.77 mL/kg and 48.1 mL/min x kg, respectively. Clinically, medetomidine significantly reduced heart rate and increased rectal temperature for 45 min. Atipamezole reversed the sedative effects of medetomidine. However, all the animals, except one, relapsed into sedation at an average of 80 min after injection of the antagonist.
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