Pharmacokinetics and pharmacodynamics of intravenous continuous rate infusion and repeated intramuscular administration of dexmedetomidine in standing horses.
Abstract: An ideal dexmedetomidine protocol has yet to be determined for standing sedation in horses. It was hypothesized that an IV bolus followed by CRI dexmedetomidine would have a quicker increase in plasma concentrations compared with repeated IM injections. In a crossover design, eight adult, female horses were randomly placed into two groups: the CRI group (IV bolus dexmedetomidine at 0.005 mg/kg followed by a CRI at 0.01 mg/kg/h for 15 min then 0.005 mg/kg/h for 60 min) and the IM group (dexmedetomidine at 0.01 mg/kg, followed by 0.005 mg/kg in 30-min intervals for 60 min). Clearance and elimination half-life were 134 ± 67.4 ml/kg/min and 44.3 ± 26.3 min, respectively, in the CRI group, and apparent clearance and half-life were 412 ± 306 ml/kg/min (Cl/F) and 38.9 ± 18.6 min, respectively, in the IM group. Analgesia was evaluated using mechanical pressure threshold. Intravenous dexmedetomidine produced faster onset of sedation and increased pressure threshold compared with IM administration. Individual horses had a large variability in dexmedetomidine plasma concentrations between CRI and IM administration. The odds of a decreased GI motility following IV administration was 12.34 times greater compared with IM administration.
© 2021 John Wiley & Sons Ltd.
Publication Date: 2021-02-12 PubMed ID: 33576078DOI: 10.1111/jvp.12951Google Scholar: Lookup
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Summary
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This study compares the effectiveness and efficiency of intravenous and intramuscular administration of dexmedetomidine for sedating standing horses. It concludes that intravenous method causes quick sedation and increased pain threshold, but also has a higher chance of reducing gastrointestinal motility.
Research Objectives and Methods
- The aim of this research was to determine the most effective use of dexmedetomidine, a sedative drug, in horses. The drug can be administered either intravenously (IV) or intramuscularly (IM), and the researchers set out to distinguish which method affords quicker drug action and increased analgesia.
- The experiment was conducted using a crossover design, where both procedures are performed on the same subject.
- Eight adult, female horses were divided randomly into two groups. One group was administered dexmedetomidine through an IV bolus protocol and the other group through repeated IM injections.
Respective Protocols of Administration
- For the IV group, an initial bolus dose of dexmedetomidine at 0.005 mg/kg was given, followed by a continuous rate infusion (CRI) at 0.01 mg/kg/h for 15 min, and then 0.005 mg/kg/h for 60 min.
- For the IM group, a dexmedetomidine initiation dose of 0.01 mg/kg was given, followed by an additional 0.005 mg/kg injection at 30-min intervals for a total of 60 min.
Study Outcomes
- For the IV group, the drug clearance time was 134 ± 67.4 ml/kg/min and the elimination half-life was 44.3 ± 26.3 min.
- For the IM group, apparent clearance and half-life were 412 ± 306 ml/kg/min and 38.9 ± 18.6 min, respectively.
- The study found that the IV method of administration resulted in a faster onset of dexmedetomidine-induced sedation and an increased analgesia, as evaluated using a mechanical pressure threshold.
- However, there was considerable variability in plasma concentrations of dexmedetomidine among individual horses, indicating distinct physiological responses to the drug based on individual constitution.
- The IV administration method was found to have a 12.34 times greater chance of causing decreased gastrointestinal motility, that is, reduced functioning of the digestive system, as compared to the IM method.
Cite This Article
APA
Shane SE, Langston VC, Wills RW, Denney WS, Knych H, Fontenot RL, Meyer RE, Natalini CC.
(2021).
Pharmacokinetics and pharmacodynamics of intravenous continuous rate infusion and repeated intramuscular administration of dexmedetomidine in standing horses.
J Vet Pharmacol Ther, 44(4), 533-543.
https://doi.org/10.1111/jvp.12951 Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, USA.
- Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, USA.
- Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, USA.
- Human Predictions, LLC, Boston, MA, USA.
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
- Department of Pathobiology and Population Medicine, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, USA.
- Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, USA.
- Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, USA.
MeSH Terms
- Administration, Intravenous / veterinary
- Animals
- Cross-Over Studies
- Dexmedetomidine
- Female
- Horses
- Infusions, Intravenous / veterinary
- Injections, Intravenous / veterinary
Grant Funding
- ACVAA Foundation Resident Grant
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Citations
This article has been cited 2 times.- Hughes M, Tobias JD. Investigation and Clinical Experience With Subcutaneous Dexmedetomidine: An Educational Focused Review With a Focus on Pediatric-Aged Patients. J Pediatr Pharmacol Ther 2025 Dec;30(6):744-751.
- Di Cesare F, Rabbogliatti V, Draghi S, Amari M, Brioschi FA, Villa R, Ravasio G, Cagnardi P. Pharmacokinetics of dexmedetomidine in anaesthetized horses following repeated subcutaneous administration and intravenous constant rate infusion. BMC Vet Res 2023 Dec 9;19(1):264.
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