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Home / Equine Research Bank / J Vet Pharmacol Ther / Pharmacokinetics and pharmacodynamics of oral and intravenou...
Journal of veterinary pharmacology and therapeutics2021; 45(2); 177-187; doi: 10.1111/jvp.13037

Pharmacokinetics and pharmacodynamics of oral and intravenous metoprolol tartrate in clinically healthy horses.

Abstract: Cardiac drugs with defined pharmacological parameters in horses are limited. The objective of this study was to characterize the pharmacokinetic properties and cardiovascular effects of intravenous and oral metoprolol tartrate (MET) in horses. In a 2-period randomized cross-over design, MET was administered IV (0.04 mg/kg) and PO (6 mg/kg) once to six healthy adult horses. Horses were monitored via continuous telemetry and non-invasive blood pressure (NIBP). Blood samples were serially collected for 72 h post-administration, and concentrations were determined by LC-MS/MS. Pharmacokinetics were modeled using a 3-compartment model and non-linear least squares regression. Median (range) MET concentration was 110 (40.1-197) ng/ml collected 1 min (0.0167 h) after a bolus IV administration. Maximum concentration (C ) after PO administration was 2135 (1590-4170) ng/ml at 0.5 (0.25-0.5) hours. Oral bioavailability was 54% (17-100%). Median apparent volume of distribution was 0.39 (0.17-0.58) l/kg, clearance was 12.63 (11.41-18.94) ml/kg/min, and elimination half-life was 21.1 (7.46-34.36) minutes. No clinically relevant effects of IV or PO metoprolol were noted on cardiac rhythm or NIBP. Sweating was the most common side effect. The metoprolol doses used in this study achieve plasma concentrations reported to achieve ß-blockade in humans.
© 2021 John Wiley & Sons Ltd.
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Publication Date: 2021-12-15 PubMed ID: 34913168DOI: 10.1111/jvp.13037Google 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 research aims to understand the effects and movement of the heart medication metoprolol tartrate in horses, when provided orally and via intravenous methods.

Objective of the Study

  • This study is designed to examine the pharmacokinetic properties of metoprolol tartrate, a drug used for cardiac conditions, in horses. Pharmacokinetics refers to the movement of drugs within the body and their biological impacts, including absorption, distribution, metabolism, and excretion.

Research Design

  • Researchers used a randomized cross-over design with two distinct periods for this study. This method involves the same sample group receiving different treatments in sequential periods, in this case, metoprolol tartrate administered orally and via intravenous methods.

Data Collection and Processing

  • Continuous telemetry was used to monitor the horses, alongside non-invasive blood pressure measurements. Telemetry is a wireless communication technique where information is measured at remote points and transmitted to receiving equipment for the purpose of monitoring.
  • Blood samples were collected at regular intervals for up to 72 hours after the administration of the drug. The concentration of metoprolol tartrate in these samples was determined using liquid chromatography-mass spectrometry (LC-MS/MS), a powerful analytical technique.
  • The pharmacokinetic properties, such as the drug’s volume of distribution, clearance rate, and elimination half-life, were modeled using a three-compartment model and non-linear least squares regression. This model enables the determination of how the drug is absorbed, distributed, and eliminated by the body.

Key Findings

  • The maximum concentration of metoprolol reached in the horses’ systems after oral administration was significantly higher than the concentration reached after intravenous administration.
  • The median apparent volume of distribution, clearance, and elimination half-life were calculated. These measurements describe how extensively the drug is distributed in the body, the efficiency of the body in eliminating the drug, and the time it takes for half of the drug to be eliminated from the body, respectively.
  • Despite reaching concentrations reported to achieve ß-blockade in humans, no significant impact was observed on the cardiac rhythm or blood pressure of the horses. This implies that the horses’ body systems may interact differently with the drug compared to humans, neutralizing its intended effects.
  • The most common side effect observed in the horses was sweating.

Cite This Article

APA
Luethy D, Robinson MA, Stefanovski D, Haughan J, Torcivia C, Kowalski A, Ford M, You Y, Missanelli J, Slack J. (2021). Pharmacokinetics and pharmacodynamics of oral and intravenous metoprolol tartrate in clinically healthy horses. J Vet Pharmacol Ther, 45(2), 177-187. https://doi.org/10.1111/jvp.13037

Publication

Journal of veterinary pharmacology and therapeutics
ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English
Volume: 45
Issue: 2
Pages: 177-187

Researcher Affiliations

Luethy, Daniela
  • Department of Clinical Studies-New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, Pennsylvania, USA.
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA.
Robinson, Mary A
  • Department of Clinical Studies-New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, Pennsylvania, USA.
  • Pennsylvania Equine Toxicology and Research Lab, School of Veterinary Medicine, University of Pennsylvania, West Chester, Pennsylvania, USA.
Stefanovski, Darko
  • Department of Clinical Studies-New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, Pennsylvania, USA.
Haughan, Joanne
  • Department of Clinical Studies-New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, Pennsylvania, USA.
Torcivia, Catherine
  • Department of Clinical Studies-New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, Pennsylvania, USA.
Kowalski, Alycia
  • Department of Clinical Studies-New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, Pennsylvania, USA.
Ford, Matthew
  • Department of Clinical Studies-New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, Pennsylvania, USA.
You, Youwen
  • Pennsylvania Equine Toxicology and Research Lab, School of Veterinary Medicine, University of Pennsylvania, West Chester, Pennsylvania, USA.
Missanelli, Jaclyn
  • Pennsylvania Equine Toxicology and Research Lab, School of Veterinary Medicine, University of Pennsylvania, West Chester, Pennsylvania, USA.
Slack, Joann
  • Department of Clinical Studies-New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, Pennsylvania, USA.

MeSH Terms

  • Administration, Oral
  • Animals
  • Area Under Curve
  • Chromatography, Liquid / veterinary
  • Cross-Over Studies
  • Half-Life
  • Horses
  • Injections, Intravenous / veterinary
  • Metoprolol / pharmacokinetics
  • Metoprolol / pharmacology
  • Tandem Mass Spectrometry / veterinary

Grant Funding

  • University of Pennsylvania Raymond Firestone Trust
  • Pennsylvania State Horse Racing Commission

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