Plasma drug concentrations and clinical effects of a peripheral alpha-2-adrenoceptor antagonist, MK-467, in horses sedated with detomidine.
Abstract: 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. Methods: Experimental randomized blinded crossover study. Methods: Six healthy horses. Methods: 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. Results: 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: 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.
© 2013 The Authors. Veterinary Anaesthesia and Analgesia © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.
Publication Date: 2013-01-31 PubMed ID: 23368795DOI: 10.1111/vaa.12012Google Scholar: Lookup
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- Journal Article
- Randomized Controlled Trial
Summary
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The research focuses on the effects of the drug MK-467 on horses that are sedated with detomidine. It highlights how MK-467 affects heart rate, gut motility and the levels of sedation in horses.
Research Methods
- The study was a randomized, blinded crossover study involving six healthy horses.
- The drug detomidine was administered alone and in combination with MK-467.
- The level of sedation and intestinal sounds were scored while heart rate and central venous pressure were measured.
- Blood was collected to determine plasma drug concentrations.
- Statistical tests (Repeated measures anova and Student’s t-test) were used to evaluate and compare heart rate, central venous pressure, intestinal sounds, area under the time-sedation curve and pharmacokinetic parameters among the treatments.
Research Findings
- No heart blocks were detected in any of the horses treated with a combination of detomidine and MK-467.
- A significant reduction in heart rate after the administration of detomidine alone was detected, while heart rate was significantly higher in horses treated with the combination of detomidine and MK-467.
- Intestinal hypomotility caused by detomidine was prevented by MK-467. Hypomotility refers to a decrease in the ability of the gut to move food through the digestive tract, hence, the improvement with MK-467 indicates better gut functionality.
- The clinical quality of detomidine-induced sedation was not affected by MK-467, although the duration of the effect was reduced, possibly due to the effects of MK-467 on the plasma concentration of detomidine.
- MK-467 affected the pharmacokinetics of detomidine by lowering the area under the plasma concentration-time curve, increasing its volume of distribution and clearance.
Conclusion
In conclusion, the study found that MK-467 has potential benefits of preventing detomidine-induced bradycardia and intestinal hypomotility in horses. This implies that the application of MK-467 may be useful clinically in preventing certain peripheral side effects of detomidine in equine healthcare. However, the duration of the sedative effect was reduced, indicating a need for further study on dosages and timing.
Cite This Article
APA
Vainionpää MH, Raekallio MR, Pakkanen SA, Ranta-Panula V, Rinne VM, Scheinin M, Vainio OM.
(2013).
Plasma drug concentrations and clinical effects of a peripheral alpha-2-adrenoceptor antagonist, MK-467, in horses sedated with detomidine.
Vet Anaesth Analg, 40(3), 257-264.
https://doi.org/10.1111/vaa.12012 Publication
Researcher Affiliations
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland. mari.vainionpaa@helsinki.fi
MeSH Terms
- Adrenergic alpha-2 Receptor Antagonists / blood
- Adrenergic alpha-2 Receptor Antagonists / pharmacokinetics
- Animals
- Area Under Curve
- Conscious Sedation / veterinary
- Cross-Over Studies
- Drug Interactions
- Female
- Gastrointestinal Motility / drug effects
- Half-Life
- Heart Rate / drug effects
- Horses / blood
- Hypnotics and Sedatives
- Imidazoles / pharmacology
- Quinolizines / blood
- Quinolizines / pharmacokinetics
Citations
This article has been cited 4 times.- Verhaar N, Kopp V, Pfarrer C, Neudeck S, König K, Rohn K, Kästner S. Alpha(2) Antagonist Vatinoxan Does Not Abolish the Preconditioning Effect of Dexmedetomidine on Experimental Ischaemia-Reperfusion Injury in the Equine Small Intestine.. Animals (Basel) 2023 Aug 30;13(17).
- Verhaar N, Hoppe S, Grages AM, Hansen K, Neudeck S, Kästner S, Mazzuoli-Weber G. Dexmedetomidine Has Differential Effects on the Contractility of Equine Jejunal Smooth Muscle Layers In Vitro.. Animals (Basel) 2023 Mar 10;13(6).
- Tapio H, Raekallio MR, Mykkänen A, Männikkö S, Scheinin M, Bennett RC, Vainio O. Effects of vatinoxan on cardiorespiratory function and gastrointestinal motility during constant-rate medetomidine infusion in standing horses.. Equine Vet J 2019 Sep;51(5):646-652.
- Pakkanen SAE, de Vries A, Raekallio MR, Mykkänen AK, Palviainen MJ, Sankari SM, Vainio OM. Changes in energy metabolism, and levels of stress-related hormones and electrolytes in horses after intravenous administration of romifidine and the peripheral α-2 adrenoceptor antagonist vatinoxan.. Acta Vet Scand 2018 May 9;60(1):27.
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