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Home / Equine Research Bank / J Vet Pharmacol Ther / Pharmacokinetics of xylazine after 2-, 4-, and 6-hr duration...
Journal of veterinary pharmacology and therapeutics2020; 43(6); 557-564; doi: 10.1111/jvp.12873

Pharmacokinetics of xylazine after 2-, 4-, and 6-hr durations of continuous rate infusions in horses.

Abstract: Intravenous (i.v.) bolus administration of xylazine (XYL) (0.5 mg/kg) immediately followed by a continuous rate infusion (CRI) of 1 mg kg  hr for 2, 4, and 6 hr produced immediate sedation, which lasted throughout the duration of the CRI. Heart rate decreased and blood pressure increased significantly (p > .05) in all horses during the first 15 min of infusion, both returned to and then remained at baseline during the duration of the infusion. Compartmental models were used to investigate the pharmacokinetics of XYL administration. Plasma concentration-time curves following bolus and CRI were best described by a one-compartment model. No differences were found between pharmacokinetic estimates of the CRIs for the fractional elimination rate constant (K ), half-life (t ), volume of distribution (V ), and clearance (Cl). Median and range were 0.42 (0.15-0.97)/hr, 1.68 (0.87-4.52) hr, 5.85 (2.10-19.34) L/kg, and 28.7 (19.6-39.5) ml min  kg , respectively. Significant differences were seen for area under the curve ( ) (p < .0002) and maximum concentration (C ) (p < .04). This indicates that with increasing duration of infusion, XYL may not accumulate in a clinically relevant way and hence no adjustments are required in a longer XYL CRI to maintain a constant level of sedation and a rapid recovery.
© 2020 John Wiley & Sons Ltd.
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Publication Date: 2020-05-18 PubMed ID: 32424949DOI: 10.1111/jvp.12873Google Scholar: Lookup
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  • Journal Article
  • Randomized Controlled Trial
  • Veterinary

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study examines the pharmacokinetics or drug absorption, distribution, metabolism, and excretion behavior of xylazine, a medication used for sedation in horses, when continuously administered intravenously at different duration intervals. The finding concludes no clinical accumulation of xylazine over longer durations of infusion, suggesting no need for dosage adjustments for prolonged treatment periods.

Research Methodology

  • Initial xylazine dosage (0.5 mg/kg) was administered as a bolus i.e. a one-time, fast intravenous injection to horses, followed by a continuous rate infusion (CRI) of 1 mg/kg/hr for time durations of 2, 4, and 6 hours.
  • The physiological response of the horses, including immediate sedation, changes in heart rate and blood pressure, was observed and recorded.
  • Compartmental models were used to analyze the pharmacokinetics of xylazine administration in horses.

Findings: Key Variables and Responses

  • The study found that the plasma concentration-time curves, indicative of how the drug behaves within the body, for bolus and CRI were best described by a one-compartment model, suggesting that the drug was distributed and eliminated in one phase or ‘compartment’ within the horse’s body.
  • Crucial pharmacokinetic parameters like the fractional elimination rate constant (how fast drug is removed from body), half-life (time it takes for the drug concentration to reduce to half its original level), volume of distribution (extent of drug spread in the body), and clearance (rate at which drug is removed from the blood) were assessed. No significant differences were found across the different time periods of CRI.
  • However, differences were seen in the area under the curve (total drug exposure over time) and the maximum concentration of the drug during the course of treatment.

Conclusion

  • Contrary to expectations, the study indicates that increasing the duration of xylazine infusion does not result in its significant accumulation in a clinically relevant manner.
  • This suggests that there is no need for adjustments in dosage during a longer xylazine CRI to maintain a constant level of sedation and ensure a rapid recovery in the horses.

Cite This Article

APA
Hopster K, Soma LR, Li X, Hopster-Iversen C, Boston RC, Driessen B. (2020). Pharmacokinetics of xylazine after 2-, 4-, and 6-hr durations of continuous rate infusions in horses. J Vet Pharmacol Ther, 43(6), 557-564. https://doi.org/10.1111/jvp.12873

Publication

Journal of veterinary pharmacology and therapeutics
ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English
Volume: 43
Issue: 6
Pages: 557-564

Researcher Affiliations

Hopster, Klaus
  • University of Pennsylvania, School of Veterinary Medicine, Kennett Square, PA, USA.
Soma, Lawrence R
  • University of Pennsylvania, School of Veterinary Medicine, Kennett Square, PA, USA.
Li, Xiaoqing
  • Pennsylvania Equine Toxicology & Research Center, West Chester University, West Chester, PA, USA.
Hopster-Iversen, Charlotte
  • Department of Large Animal Sciences, Faculty of Life Sciences, University of Copenhagen, Taastrup, Denmark.
Boston, Raymond C
  • University of Pennsylvania, School of Veterinary Medicine, Kennett Square, PA, USA.
Driessen, Bernd
  • University of Pennsylvania, School of Veterinary Medicine, Kennett Square, PA, USA.

MeSH Terms

  • Animals
  • Area Under Curve
  • Cross-Over Studies
  • Drug Administration Schedule
  • Female
  • Half-Life
  • Horses / blood
  • Horses / metabolism
  • Hypnotics and Sedatives / blood
  • Hypnotics and Sedatives / pharmacokinetics
  • Injections, Intravenous
  • Male
  • Xylazine / blood
  • Xylazine / pharmacokinetics

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