A pharmacokinetic study including some relevant clinical effects of medetomidine and atipamezole in lactating dairy cows

Medetomidine is the most potent and selective alpha(2)-agonist used in vete rinary medicine and its effects can be antagonized by the alpha(2)-antagoni st atipamezole. The pharmacokinetics of medetomidine and atipamezole were s tudied in a crossover trial in eight lactating dairy cows. The animals were injected intravenously (i.v,) with medetomidine (40 mu g/kg) followed by a tipamezole i.v. (200 mu g/kg) or saline i.v, after 60 min. Drug concentrati ons in plasma were measured by HPLC. After the injection of atipamezole, th e concentration of medetomidine in plasma increased slightly, the mean incr ement 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 i ncrease in medetomidine concentration is caused by displacement of medetomi dine by atipamezole in highly perfused tissues, The volume of distribution at steady state (V-ss) 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.kg. V-ss and Cl value s for atipamezole were 1.77 mL/kg and 48.1 ml/min.kg, respectively. Clinica lly, medetomidine significantly reduced heart rate and increased rectal tem perature for 45 min. Atipamezole reversed the sedative effects of medetomid ine. However, all the animals, except one, relapsed into sedation at an ave rage of 80 min after injection of the antagonist.