Pharmacokinetics of maropitant citrate after oral administration of multiple doses in adult horses.
Abstract: The neurokinin-1 (NK-1) receptor antagonist, maropitant citrate, mitigates nausea and vomiting in dogs and cats. Nausea is poorly understood in horses, and clinical use of NK-1 receptor antagonists has not been reported. This study aimed to determine the pharmacokinetics and safety of maropitant after administration of multiple doses. We hypothesized that maropitant concentrations would be similar at steady state to those reported in dogs, with minimal adverse effects. Maropitant was administered at 4 mg/kg orally, once daily for 5 days in seven adult horses. Serial plasma maropitant concentrations were measured by liquid chromatography-mass spectrometry. Noncompartmental pharmacokinetic parameters were determined. The maximum, minimum, and average concentrations of maropitant achieved at steady state were 375.5 ± 200, 16.8 ± 7.7, and 73.5 ± 45.1 ng/ml, respectively. The terminal elimination half-life was 11.6 ± 1.4 hr, and the accumulation index was 1.3 ± 0.07. Heart rate decreased between Day 1 and Day 5 (p = .005), with three horses having heart rates of 20 beats per minute and atrioventricular block on Day 5. Pharmacokinetics of repeated maropitant administration suggests the drug could be considered for use in healthy horses. Further investigation on the clinical relevancy of its cardiac effects is warranted.
© 2020 John Wiley & Sons Ltd.
Publication Date: 2020-02-17 PubMed ID: 32067245DOI: 10.1111/jvp.12844Google Scholar: Lookup
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- Clinical Trial
- Veterinary
- Journal Article
- Adult Horses
- Adverse Effects
- Biological Half-Life
- Clinical Findings
- Clinical Pathology
- Clinical Study
- Drug
- Equine Diseases
- Equine Health
- Heart Rate
- High-performance Liquid Chromatography (HPLC)
- Oral Administration
- Pharmaceuticals
- Pharmacodynamics
- Pharmacokinetics
- Plasma
- Veterinary Medicine
- Veterinary Procedure
- Veterinary Research
Summary
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The research article describes a study on the effects of maropitant citrate, a neurokinin-1 receptor antagonist commonly used to control nausea in small animals, when administered in multiple doses to adult horses. The study aimed to understand the safety and pharmacokinetic profile of the drug in horses in the hope it might be usefully applied in equine nausea management.
Objective of the Research
- The main objective of this study was to assess the pharmacokinetics (the movement of a drug within the body) and safety of maropitant citrate, a drug used to treat nausea and vomiting in small animals, after its administration in multiple doses to adult horses. The researchers wanted to see if maropitant concentrations would be similar to the concentrations observed in dogs, and whether the drug would cause any adverse effects in horses.
Methodology
- The study was conducted on seven adult horses.
- Each horse received 4 mg/kg of maropitant orally once a day for five consecutive days.
- The researchers collected blood samples from the horses at regular intervals, which were then analyzed using liquid chromatography-mass spectrometry to determine plasma maropitant concentrations.
- Noncompartmental pharmacokinetic parameters were determined to study the drug’s absorption, distribution, metabolism, and excretion in the horses’ bodies. The parameters calculated included maximum, minimum, and average concentrations of maropitant achieved at steady state, terminal elimination half-life, and accumulation index.
Findings
- The maximum, minimum, and average concentrations of maropitant at a steady state in the horse’s blood were 375.5 ± 200, 16.8 ± 7.7, and 73.5 ± 45.1 ng/ml, respectively.
- The drug’s terminal elimination half-life was found to be 11.6 ± 1.4 hours while the accumulation index was calculated to be 1.3 ± 0.07. The terminal elimination half-life measures the time it takes for the concentration of the drug in the body to decrease by half, which provides an idea about how long the effect of the drug will last. The accumulation index is used to estimate the extent of drug accumulation during chronic dosing.
- The horses experienced a decrease in heart rate between Day 1 and Day 5, with three of them showing a decrease of 20 beats per minute and atrioventricular block (delay or complete block in the transmission of electrical pulses from the atria to the ventricles) on Day 5.
Conclusion
- The findings indicate that maropitant citrate might have potential for use in managing nausea in horses, considering its pharmacokinetic profile. However, its cardiac effects observed in this study warrant further investigation before it can be safely recommended for clinical use in horses.
Cite This Article
APA
Berryhill EH, Knych H, Chigerwe M, Edman J, Magdesian KG.
(2020).
Pharmacokinetics of maropitant citrate after oral administration of multiple doses in adult horses.
J Vet Pharmacol Ther, 43(3), 282-287.
https://doi.org/10.1111/jvp.12844 Publication
Researcher Affiliations
- Department of Veterinary Medicine and Epidemiology, University of California, Davis, CA, USA.
- Kenneth L. Maddy Equine Analytical Chemistry Laboratory, University of California, Davis, CA, USA.
- Department of Veterinary Medicine and Epidemiology, University of California, Davis, CA, USA.
- Department of Veterinary Medicine and Epidemiology, University of California, Davis, CA, USA.
- Department of Veterinary Medicine and Epidemiology, University of California, Davis, CA, USA.
MeSH Terms
- Administration, Oral
- Animals
- Antiemetics / administration & dosage
- Antiemetics / blood
- Antiemetics / pharmacokinetics
- Area Under Curve
- Drug Administration Schedule
- Female
- Half-Life
- Horses / blood
- Horses / metabolism
- Male
- Quinuclidines / administration & dosage
- Quinuclidines / blood
- Quinuclidines / pharmacokinetics
Grant Funding
- X0GMEC / Henry Endowed Chair in Emergency Medicine and Critical Care
- 3-V435CEH / Center for Equine Health with contributions from the Oak Tree Racing Association
- University of California, Davis
- State of California pari-mutuel wagering fund
References
This article includes 13 references
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