Plasma and urine pharmacokinetics of hydroxyzine and cetirizine following repeated oral administrations to exercised horses

Paine, Stuart W.; Aldurdunji, Mohammed; Garth-Greeves, Alix; Muir, Tessa; Hincks, Pamela R.

Abstract

Hydroxyzine and cetirizine are first- and second-generation oral antihistamine drugs, respectively, used to treat allergic reactions in horses. Cetirizine is also a metabolite of hydroxyzine, which may lead to complexities in regulating their use in equine sporting events. The aim of the research was to be able to provide detection times (DT) from pharmacokinetic studies in thoroughbred horses to better inform trainers, and their veterinary surgeons, prescribing these substances for treatment of Thoroughbred racehorses. Six and two horses were given 9 repeated administrations of hydroxyzine HCl (500mg BID) or cetirizine HCl (190mg BID), respectively. Plasma and urine hydroxyzine and cetirizine concentrations were measured by liquid chromatography–tandem mass spectrometry (LC-MS/MS). A holistic non-linear mixed effects PK model was developed that described both plasma and urine concentrations of hydroxyzine and cetirizine, either from administration of each individually or cetirizine as a metabolite of hydroxyzine. Using the parameters obtained from this PK model in conjunction with methodology developed by Toutain afforded possible screening limits (SL) that can regulate for a DT of 4days in either plasma or urine. Hydroxyzine and cetirizine concentration prediction intervals for the 80th, 95th and 99th percentiles of a virtual horse population were performed in order to assess the statistical protection of the DT. However, it is down to the individual racing authorities to apply their own risk management.

Citation

Paine, S. W., Aldurdunji, M., Garth-Greeves, A., Muir, T., & Hincks, P. R. (2022). Plasma and urine pharmacokinetics of hydroxyzine and cetirizine following repeated oral administrations to exercised horses. Journal of Veterinary Pharmacology and Therapeutics, 45(1), 46-53. https://doi.org/10.1111/jvp.13010

• Journal Article Type: Article
• Acceptance Date: Aug 21, 2021
• Online Publication Date: Sep 1, 2021
• Publication Date: Jan 1, 2022
• Deposit Date: Aug 31, 2021
• Publicly Available Date: Sep 2, 2022
• Journal: Journal of Veterinary Pharmacology and Therapeutics
• Print ISSN: 0140-7783
• Electronic ISSN: 1365-2885
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 45
• Issue: 1
• Pages: 46-53
• DOI: https://doi.org/10.1111/jvp.13010
• Keywords: General Veterinary; Pharmacology
• Public URL: https://nottingham-repository.worktribe.com/output/6137527
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1111/jvp.13010
• Additional Information: This is the peer reviewed version of the following article: Paine, S. W., Aldurdunji, M., Garth-Greeves, A., Muir, T., & Hincks, P. R. (2022). Plasma and urine pharmacokinetics of hydroxyzine and cetirizine following repeated oral administrations to exercised horses. Journal of Veterinary Pharmacology and Therapeutics, 45, 46– 53, which has been published in final form at https://doi.org/10.1111/jvp.13010. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.