Pharmacokinetics of hydroxyzine and cetirizine following oral administration of hydroxyzine to exercised Thoroughbred horses.
Abstract: Hydroxyzine is a first-generation antihistamine and cetirizine, a second-generation antihistamine and active metabolite of hydroxyzine. Hydroxyzine is commonly used in performance horses and as such its use in closely regulated; however, there are no published studies suitable for establishing appropriate regulatory recommendations. In the current study, 12 exercised Thoroughbred research horses received a single oral administration of 500 mg of hydroxyzine. Blood and urine samples were collected prior to and up to 96 hr postdrug administration and concentrations of hydroxyzine and cetirizine determined using liquid chromatography-tandem mass spectrometry. A joint parent/metabolite population 2-compartment pharmacokinetic model with first-order absorption and elimination was utilized to describe the pharmacokinetics of both compounds. Serum hydroxyzine and cetirizine concentrations were above the limit of quantitation (0.1 ng/ml) of the assay at 96 hr (the last time point sampled). The terminal half-life was 7.41 and 7.13 hr for hydroxyzine and cetirizine, respectively. Findings from this study suggest that a prolonged withdrawal time should be observed if this compound is used in performance administered to performance horses and is classified as prohibited substance by the applicable regulatory body.
© 2019 John Wiley & Sons Ltd.
Publication Date: 2019-09-06 PubMed ID: 31490561DOI: 10.1111/jvp.12808Google Scholar: Lookup
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- Journal Article
Summary
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The research article examines how hydroxyzine, a commonly-used antihistamine in performance horses, and its metabolite, cetirizine, behave within the horse’s body following administration, in order to guide regulatory rules related to doping in horse racing.
Details of the Experiment
- The study was conducted on twelve thoroughbred horses which were part of an exercise regimen.
- A single oral dose of 500mg of hydroxyzine was administered to each horse.
- Both blood and urine samples were collected from the horses before and multiple times up to 96 hours after the administration of the drug.
Detection Mechanism
- The research utilized a tool called liquid chromatography-tandem mass spectrometry to determine the concentrations of hydroxyzine and cetirizine in the samples.
- This resulted in a two-section pharmacokinetic model for each drug, reflecting their absorption and elimination patterns in the horse’s body.
Key Findings
- The compounds were detectable at the lowest measureable concentration of the assay (0.1 ng/ml), even 96 hours (4 days) following administration. This suggests that these drugs stay in the horse’s system for an extended period of time.
- The half-lives of hydroxyzine and cetirizine were found to be approximately 7.41 hours and 7.13 hours, respectively. This term refers to the time it takes for the concentration of the drug in the body to reduce to half its original value.
- According to these results, the researchers suggest that a sufficiently long withdrawal period should be observed if hydroxyzine is given to a performance horse, since a significant amount of the drug can remain in the horse’s body days after its administration. This is particularly relevant as many animal sports governing bodies classify hydroxyzine as a banned substance.
Cite This Article
APA
Knych HK, Weiner D, Steinmetz S, Flynn K, McKemie DS.
(2019).
Pharmacokinetics of hydroxyzine and cetirizine following oral administration of hydroxyzine to exercised Thoroughbred horses.
J Vet Pharmacol Ther, 42(6), 617-623.
https://doi.org/10.1111/jvp.12808 Publication
Researcher Affiliations
- K.L. Maddy Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, California.
- Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California.
- Pharmacometrics Consultant, Chapel Hill, North Carolina.
- K.L. Maddy Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, California.
- California Department of Food and Agriculture, Animal Health Branch, Sacramento, California.
- K.L. Maddy Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, California.
MeSH Terms
- Administration, Oral
- Animals
- Area Under Curve
- Cetirizine / administration & dosage
- Cetirizine / blood
- Cetirizine / metabolism
- Cetirizine / pharmacokinetics
- Half-Life
- Histamine H1 Antagonists / administration & dosage
- Histamine H1 Antagonists / blood
- Histamine H1 Antagonists / metabolism
- Histamine H1 Antagonists / pharmacokinetics
- Horses / blood
- Horses / metabolism
- Hydroxyzine / administration & dosage
- Hydroxyzine / blood
- Hydroxyzine / metabolism
- Hydroxyzine / pharmacokinetics
Grant Funding
- California Department of Food and Agriculture's Equine Medication Monitoring Program
- California Horse Racing Board
References
This article includes 11 references
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