Pharmacokinetics of medetomidine

Abstract

The pharmacokinetics of medetomidine administered as a single dose (80 micrograms/kg) were studied in rat, dog and cat with the tritium labelled drug. The results showed a rapid distribution, after an s.c. dose, of medetomidine radioactivity into rat tissues including the brains. In plasma/serum a distribution phase with a half-life of only a few minutes was observed. Peak concentration after i.m. administration (dog & cat) was seen within 0.5 h in complete accordance with the rapid onset of clinical effects. The apparent volumes of distribution ranged from 2.8 (dog, i.v.) to 3.5 l/kg (cat, i.m.) and clearances from 27.5 (dog, i.m.) to 33.4 ml/min kg (dog, i.v.). Elimination of medetomidine from plasma/serum occurred with half-lives ranging from 0.97 to 1.60 h. Differences between dosing routes were small. Elimination of radioactivity from rat brain tissue followed approximately the same time course as elimination from plasma suggesting that termination of clinical effects is controlled by removal of drug from CNS. Excretion of radioactivity was from 28.6 to 74.7% of the dose in three days. In each species most of the activity was excreted in urine. Fecal excretion was significant only in the rat. No measurable levels of the parent drug were found in excreta. Instead a hydroxylated product(s) and (their) conjugates (except in the cat) were present in urine. Other metabolites were not identified. It was concluded that elimination occurs mainly by biotransformation in the liver.