Simulation of the sedative effect of high doses of detomidine in equines

Abstract

The objective of the study was to simulate the sedative effect of the administration of detomidine in doses of 80 ug/kg by intravenous and intramuscular route in equines. A pharmacokinetic/pharmacodynamic (PK/PD) model was performed with the sigmoid curve of plasma concentration, obtained by Mama and collaborators, depending on the effect on the head position by means of Hill equation. A sedative effect simulation of 80 ug/kg intravenous (IV) and intramuscular (IM) doses by Hill's equation was then performed. Higher and prolonged plasmatic concentrations were obtained after administrations of 80 ug/kg, when compared to administrations of 30 ug/kg resulting in higher and longer effect. The simulation of the effect of detomidine after administration of 80 ug/kg IV determined effects in the head height higher than 90%, 75% and 50% up to 2, 4 and 6 hours after administration. Meanwhile, the simulation of the effect of detomidine after the administration of 80 ug/kg IM determined effects in head height higher than 90%, 75% and 50% up to 3, 4 and 6 hours after administration. The present simulation showed that the effects of the position of the head after the administration of 80 ug/kg of detomidine via IV and IM in equines are superior and more prolonged when compared to the administration of 30 ug/kg. Therefore, in vivo studies should be performed in order to verify the adverse effects of these dosages in equines.