Plasma drug concentrations and clinical effects of a peripheral alpha-2-adrenoceptor antagonist, MK-467, in horses sedated with detomidine
Article first published online: 31 JAN 2013
© 2013 The Authors. Veterinary Anaesthesia and Analgesia © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia
Veterinary Anaesthesia and Analgesia
Volume 40, Issue 3, pages 257–264, May 2013
How to Cite
Vainionpää, M. H., Raekallio, M. R., Pakkanen, S. A., Ranta-Panula, V., Rinne, V. M., Scheinin, M. and Vainio, O. M. (2013), Plasma drug concentrations and clinical effects of a peripheral alpha-2-adrenoceptor antagonist, MK-467, in horses sedated with detomidine. Veterinary Anaesthesia and Analgesia, 40: 257–264. doi: 10.1111/vaa.12012
- Issue published online: 12 APR 2013
- Article first published online: 31 JAN 2013
- Manuscript Accepted: 13 OCT 2012
- Manuscript Received: 11 JUN 2012
- gut motility;
To investigate plasma drug concentrations and the effect of MK-467 (L-659′066) on sedation, heart rate and gut motility in horses sedated with intravenous (IV) detomidine.
Experimental randomized blinded crossover study.
Six healthy horses.
Detomidine (10 μg kg−1 IV) was administered alone (DET) and in combination with MK-467 (250 μg kg−1 IV; DET + MK). The level of sedation and intestinal sounds were scored. Heart rate (HR) and central venous pressure (CVP) were measured. Blood was collected to determine plasma drug concentrations. Repeated measures anova was used for HR, CVP and intestinal sounds, and the Student's t-test for pairwise comparisons between treatments for the area under the time-sedation curve (AUCsed) and pharmacokinetic parameters. Significance was set at p < 0.05.
A significant reduction in HR was detected after DET, and HR was significantly higher after DET + MK than DET alone. No heart blocks were detected in any DET + MK treated horses. DET + MK attenuated the early increase in CVP detected after DET, but later the CVP decreased with both treatments. Detomidine-induced intestinal hypomotility was prevented by MK-467. AUCsed was significantly higher with DET than DET + MK, but maximal sedations scores did not differ significantly between treatments. MK-467 lowered the AUC of the plasma concentration of detomidine, and increased its volume of distribution and clearance.
Conclusions and clinical relevance
MK-467 prevented detomidine induced bradycardia and intestinal hypomotility. MK-467 did not affect the clinical quality of detomidine-induced sedation, but the duration of the effect was reduced, which may have been caused by the effects of MK-467 on the plasma concentration of detomidine. MK-467 may be useful clinically in the prevention of certain peripheral side effects of detomidine in horses.