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

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.

Jugular venous pooling during lowering of the head affects blood pressure of the anesthetized giraffe

“…To avoid influence of the induction agents (medetomidine and etorphine) on the vascular measurements by artificially elevating blood pressures, the effects were antagonized with naltrexone, and measurements were started Ͼ 90 min following its administration by which time the effects of ketamine would be minimal (32,40).…”

The impact ofMK‐467 on plasma drug concentrations, sedation and cardiopulmonary changes in sheep treated with intramuscular medetomidine and atipamezole for reversal

“…However, relapses into sedation (i.e. resedation after an initial recovery) have been reported in some ruminant species (Ranheim, Arnemo, Ryeng, Soli, & Horsberg, ; Ranheim, Soli, Ryeng, Arnemo, & Horsberg, ; Ranheim et al., ). In addition, ATI did not completely reverse medetomidine‐induced hypoxaemia in sheep (Ko & McGrath, ; Talke et al., ).…”

Medetomidine and atipamezole in sheep: disposition and clinical effects

“…The pharmacokinetics of medetomidine have been described previously in sheep (Muge et al, 1996); however, the pharmacokinetics of medetomidine followed by atipamezole, and atipamezole have not been studied in this species. An interaction between medetomidine and atipamezole has previously been described in reindeer, dairy calves and dairy cows, in all of which the injection of atipamezole caused the plasma concentration of medetomidine to rise (Ranheim et al, 1997(Ranheim et al, , 1998(Ranheim et al, , 1999. An interaction between the agonist and the antagonist has also been described in dogs, in which atipamezole increased clearance of medetomidine (Salonen et al, 1995).…”