Pharmacokinetics of hydroxyzine and cetirizine following oral administration of hydroxyzine to exercised Thoroughbred horses

Heather K Knych, Daniel Weiner, Stacy Steinmetz, Katherine Flynn, Daniel S. McKemie

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalJournal of Veterinary Pharmacology and Therapeutics
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Hydroxyzine
Cetirizine
oral administration
antihistamines
pharmacokinetics
Horses
Oral Administration
Pharmacokinetics
horses
metabolites
blood serum
liquid chromatography
half life
urine
Non-Sedating Histamine H1 Antagonists
blood
assays
Histamine Antagonists
Tandem Mass Spectrometry
Liquid Chromatography

Keywords

  • cetirizine
  • hydroxyzine
  • pharmacokinetic modeling,metabolism
  • racehorse

ASJC Scopus subject areas

  • Pharmacology
  • veterinary(all)

Cite this

Pharmacokinetics of hydroxyzine and cetirizine following oral administration of hydroxyzine to exercised Thoroughbred horses. / Knych, Heather K; Weiner, Daniel; Steinmetz, Stacy; Flynn, Katherine; McKemie, Daniel S.

In: Journal of Veterinary Pharmacology and Therapeutics, 01.01.2019.

Research output: Contribution to journalArticle

@article{6742c7031a024d259b928f73fb83c3dd,
title = "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.",
keywords = "cetirizine, hydroxyzine, pharmacokinetic modeling,metabolism, racehorse",
author = "Knych, {Heather K} and Daniel Weiner and Stacy Steinmetz and Katherine Flynn and McKemie, {Daniel S.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1111/jvp.12808",
language = "English (US)",
journal = "Journal of Veterinary Pharmacology and Therapeutics",
issn = "0140-7783",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Pharmacokinetics of hydroxyzine and cetirizine following oral administration of hydroxyzine to exercised Thoroughbred horses

AU - Knych, Heather K

AU - Weiner, Daniel

AU - Steinmetz, Stacy

AU - Flynn, Katherine

AU - McKemie, Daniel S.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - cetirizine

KW - hydroxyzine

KW - pharmacokinetic modeling,metabolism

KW - racehorse

UR - http://www.scopus.com/inward/record.url?scp=85072082095&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85072082095&partnerID=8YFLogxK

U2 - 10.1111/jvp.12808

DO - 10.1111/jvp.12808

M3 - Article

C2 - 31490561

AN - SCOPUS:85072082095

JO - Journal of Veterinary Pharmacology and Therapeutics

JF - Journal of Veterinary Pharmacology and Therapeutics

SN - 0140-7783

ER -