ATIPAMEZOLE INCREASES MEDETOMIDINE CLEARANCE IN THE DOG - AN AGONIST-ANTAGONIST INTERACTION

Medetomidine, an alpha(2)-adrenoceptor agonist, is a potent sedative a nd analgesic agent in the dog, When necessary, its action can be effec tively antagonized by atipamezole. The present work was designed to st udy the effects of these drugs on each others' pharmacokinetics when a single intramuscular dose of medetomidine (50 mu g kg(-1)) was follow ed by a dose of atipamezole (250 mu g kg(-)1), Three different treatme nts were used: medetomidine alone, atipamezole alone, and atipamezole after medetomidine, Drug concentrations in plasma were measured by GC- MS, Statistical analysis of the results (ANOVA) revealed significant d ifferences between treatments in the kinetic parameters of medetomidin e. Atipamezole decreased the AUC of medetomidine from 41.3 to 28,6 ng h ml(-1) (P = 0.005), t(1/2) from 1,44 to 0,87 h (P = 0.015), and incr eased Cl from 21 to 31 mi min(-1) kg(-1) (P = 0.017). Differences in V -z did not reach statistical significance, The only statistically sign ificant effects of medetomidine on the pharmacokinetics of atipamezole in this study were the slight decrease of Cl and C-max as well as the increase of AUC, It is suggested that the large dose of medetomidine used caused haemodynamic changes, resulting in decreased hepatic circu lation and slower drug metabolism, Antagonism by atipamezole restored the hepatic blood now and, consequently, increased the elimination of medetomidine by biotransformation.