Pharmacokinetics of medetomidine and atipamezole in dairy calves: an agonist-antagonist interaction.
Medetomidine and atipamezole are licensed for use in dogs and cats in several countries and are highly selective and specific alpha2-adrenoceptor agents. The pharmacokinetics of the agonist medetomidine and the antagonist atipamezole were studied in a cross-over trial in eight dairy calves. The animals were injected intravenously (i.v.) with medetomidine (40 microg/kg i.v.), followed by atipamezole (200 microg/kg i.v.) or saline after 60 min. The wash-out period between experiments was 1 week. Drug concentrations in plasma were determined using HPLC. Atipamezole significantly (P < 0.05) increased the AUMC and MRT of medetomidine due to an increase in the medetomidine concentration when atipamezole was injected i.v. The mean increment in medetomidine concentration was 6.4 ng/mL, increased levels having a mean duration of 39.4 min. Other pharmacokinetic parameters of medetomidine were not significantly altered by atipamezole. Sedative effects of the agonist, and the effectiveness of the antagonist were recorded. All the animals relapsed into sedation on average 80 min after reversal with atipamezole. It is likely that the increase in medetomidine concentration after the injection of atipamezole i.v. results from displacement of medetomidine from alpha2-adrenoceptors in highly perfused tissues.
Ranheim
B
B
Department of Pharmacology, Microbiology and Food Hygiene, The Norwegian School of Veterinary Science, Oslo. Birgit.Ranheim@veths.no
Søli
N E
NE
Ryeng
K A
KA
Arnemo
J M
JM
Horsberg
T E
TE
D000316:Adrenergic alpha-Agonists / Q000493:pharmacokinetics*; D000317:Adrenergic alpha-Antagonists / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D002417:Cattle / Q000097:blood / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004336:Drug Antagonism; D005260:Female; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics*; D007093:Imidazoles / Q000493:pharmacokinetics*; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D020926:Medetomidine
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D006993:Hypnotics and Sedatives; D007093:Imidazoles; C050701:atipamezole; D020926:Medetomidine