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Journal of veterinary pharmacology and therapeutics2026; doi: 10.1111/jvp.70040

Pharmacokinetics of Topical Administration of Altrenogest in Mares and Implications for Human Health.

Abstract: Altrenogest is a synthetic progestogen widely used in equine reproductive management. Adverse effects to altrenogest have been reported in people with cutaneous exposure reported as the highest exposure pathway. Despite these reports, there has been no quantitative research to determine the capacity for altrenogest to be absorbed through skin. This study aimed to determine if cutaneous application of oral altrenogest results in systemic absorption in mares and to evaluate the influence of application site. A randomized, two-period, two-treatment crossover study was undertaken in eight mares. Mares received a topical application of oral altrenogest (0.044 mg/kg) onto clipped skin on either the neck or back for five consecutive days, with blood sampling immediately before and 1 h after each treatment. Following the final dose, blood samples were taken at 0.08, 0.16, 0.3, 0.5, 0.66, 0.83, 1, 1.5, 2, 4, 6, 8, 12, 24 and 48 h. After a 3-week washout period mares underwent treatment on the alternative site, sampling at the same intervals. Plasma samples were analysed for altrenogest using LC-MS/MS and pharmacokinetic variables were estimated using noncompartmental analysis. Altrenogest was detectable in plasma following application at both sites. Peak plasma concentrations (C) were significantly higher following neck application (1.7 ± 0.7 ng/mL) compared to the back (0.6 ± 0.3 ng/mL; p = 0.002). Concentrations remained quantifiable throughout the 48-h post-treatment period. As altrenogest is absorbed through equine skin of varying thickness, there is a need for cautious use and handling, especially given that human skin is thinner than equine skin.
© 2026 The Author(s). Journal of Veterinary Pharmacology and Therapeutics published by John Wiley & Sons Ltd.
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Publication Date: 2026-02-26 PubMed ID: 41744272DOI: 10.1111/jvp.70040Google Scholar: Lookup
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  • Journal Article

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.

Overview

  • This research investigated whether altrenogest, a hormone used in horse reproductive management, can be absorbed into the bloodstream through topical (skin) application in mares and how the site of application affects absorption.
  • The findings suggest significant absorption through horse skin, especially on the neck, raising concerns about potential human exposure through skin contact.

Background and Purpose

  • Altrenogest is a synthetic progestogen commonly used in managing reproduction in horses.
  • There have been reports of adverse effects in humans due to skin exposure to altrenogest, but no quantitative studies were available to show how much altrenogest is absorbed via the skin.
  • This study aimed to determine if topical application of an oral altrenogest formulation results in systemic absorption in mares, and whether the site of application (neck or back) influences absorption rates.

Study Design

  • A randomized, two-period, two-treatment crossover study was conducted with eight mares.
  • Each mare received altrenogest topically on clipped skin at two different sites: the neck and the back.
  • The dose applied was 0.044 mg per kg of body weight, each day for five consecutive days.
  • Blood samples were taken immediately before and one hour after each treatment to monitor altrenogest plasma levels.
  • After the last dose, further samples were collected at multiple time points spreading up to 48 hours to determine pharmacokinetic profiles.
  • A washout period of three weeks was followed, after which the mares were treated on the alternative site, with identical sampling schedules.

Methods of Analysis

  • Plasma samples were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), a sensitive method for detecting altrenogest concentrations.
  • Pharmacokinetic variables, such as peak plasma concentration (Cmax), were estimated using noncompartmental analysis, a standard approach in pharmacokinetics that does not assume a specific compartmental model.

Results

  • Altrenogest was detectable in the plasma following topical application at both the neck and back sites.
  • Peak plasma concentrations were significantly higher after application on the neck (1.7 ± 0.7 ng/mL) compared to the back (0.6 ± 0.3 ng/mL), with a p-value of 0.002 indicating statistical significance.
  • Altrenogest concentrations remained measurable for up to 48 hours after the final dose, suggesting sustained systemic presence.

Implications

  • The study confirms that altrenogest can penetrate the skin barrier in horses and enter systemic circulation, even though horse skin is generally thicker than human skin.
  • Because human skin is thinner, the potential for systemic absorption and adverse effects may be even greater in humans on accidental or occupational skin exposure.
  • These findings highlight the importance of cautious handling practices when using altrenogest, particularly avoiding skin contact and ensuring protective measures for handlers of the drug.

Summary

  • This study provides direct evidence of altrenogest absorption through the skin in mares, influenced by the site of application.
  • The results raise concerns regarding human exposure risks, emphasizing the need for safety precautions to prevent unintended systemic absorption via skin contact.
  • The research contributes important pharmacokinetic data that can help guide safer veterinary drug administration and inform occupational health standards.

Cite This Article

APA
Loy J, Sornalingam K, Cawley A, Scrivener C, Keledjian J, Noble GK. (2026). Pharmacokinetics of Topical Administration of Altrenogest in Mares and Implications for Human Health. J Vet Pharmacol Ther. https://doi.org/10.1111/jvp.70040

Publication

Journal of veterinary pharmacology and therapeutics
ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English

Researcher Affiliations

Loy, Jaymie
  • School of Agricultural, Environmental and Veterinary Sciences, Charles Sturt University, Wagga Wagga, New South Wales, Australia.
Sornalingam, Kireesan
  • Forensic and Toxicology Laboratory, NSW Heath Pathology, Sydney, Australia.
  • Australian Racing Forensic Laboratory, Racing NSW, Sydney, Australia.
Cawley, Adam
  • Racing Analytical Services Limited, Flemington, Victoria, Australia.
Scrivener, Colin
  • School of Agricultural, Environmental and Veterinary Sciences, Charles Sturt University, Wagga Wagga, New South Wales, Australia.
Keledjian, John
  • Australian Racing Forensic Laboratory, Racing NSW, Sydney, Australia.
Noble, Glenys K
  • School of Agricultural, Environmental and Veterinary Sciences, Charles Sturt University, Wagga Wagga, New South Wales, Australia.

Grant Funding

  • 0000102436 / Agrifutures Australia

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