FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
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.
Get Full Text
Publication Date: 2026-02-26 PubMed ID: 41744272DOI: 10.1111/jvp.70040Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • 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

References

This article includes 33 references
  1. Alzamzami AA, Ibrahim MMA, Nemer FMA. Personal Protective Equipment Usage and Compliance Among Healthcare Workers. International Journal of Community Medicine and Public Health 12, no. 2: 1016–1020.
    doi: 10.18203/2394‐6040.ijcmph20250043google scholar: lookup
  2. Barry BW. Novel Mechanisms and Devices to Enable Successful Transdermal Drug Delivery. European Journal of Pharmaceutical Sciences 14, no. 2: 101–114.
    doi: 10.1016/s0928‐0987(01)00167‐1google scholar: lookup
  3. Becker MH. The Health Belief Model and Sick Role Behavior. Health Education Monographs 2, no. 4: 409–419.
    doi: 10.1177/109019817400200407google scholar: lookup
  4. Bizley SC, Dudhia J, Smith RKW, Williams AC. Transdermal Drug Delivery in Horses: An In Vitro Comparison of Skin Structure and Permeation of Two Model Drugs at Various Anatomical Sites. Veterinary Dermatology 34, no. 3: 235–245.
    doi: 10.1111/vde.13162google scholar: lookup
  5. Clavijo RI, Hsiao W. Update on Male Reproductive Endocrinology. Translational Andrology and Urology 7, no. Suppl 3: S367–s372.
    doi: 10.21037/tau.2018.03.25google scholar: lookup
  6. Ellis KE, Council‐Troche RM, Von Dollen KA. Pharmacokinetics of Intrarectal Altrenogest in Horses. Journal of Equine Veterinary Science 72: 41–46.
    doi: 10.1016/j.jevs.2018.10.001google scholar: lookup
  7. European Medicines Agency. Committee for Medicinal Products for Veterinary Use. .
  8. Fedorka CE, Troedsson MHT. The Use of Progestins in Equine Medicine: A Review. Equine Veterinary Education 33, no. 9: 494–504.
    doi: 10.1111/eve.13332google scholar: lookup
  9. George J, Shafqat N, Verma R, Patidar AB. Factors Influencing Compliance With Personal Protective Equipment (PPE) Use Among Healthcare Workers. Cureus 15, no. 2: e35269.
    doi: 10.7759/cureus.35269google scholar: lookup
  10. Hornberger K, Lyman CC, Baldrighi JM, Holyoak GR. Plasma Altrenogest Concentrations in Mares After Intrarectal or Intravaginal Administration. Clinical Theriogenology 11, no. 1: 59–65.
    doi: 10.58292/ct.v10.10015google scholar: lookup
  11. Knych HK, Arthur RM, Gretler SR, McKemie DS, Goldin S, Kass PH. Pharmacokinetics of Transdermal Flunixin Meglumine and Effects on Biomarkers of Inflammation in Horses. Journal of Veterinary Pharmacology and Therapeutics 44, no. 5: 745–753.
    doi: 10.1111/jvp.12993google scholar: lookup
  12. Lee Y, Hwang K. Skin Thickness of Korean Adults. Surgical and Radiologic Anatomy 24, no. 3: 183–189.
    doi: 10.1007/s00276‐002‐0034‐5google scholar: lookup
  13. Loy J, Cawley A, Sornalingam K, Scrivener CJ, Keledjian J, Noble GK. Pharmacokinetics of Two Formulations of Altrenogest Administered to Mares. Drug Testing and Analysis 17: 1034–1040.
    doi: 10.1002/dta.3796google scholar: lookup
  14. McConaghy FF, Black L, Colgan S, Morris LH. Studies of the Pharmacokinetic Profile, In Vivo Efficacy and Safety of Injectable Altrenogest for the Suppression of Oestrus in Mares. Australian Veterinary Journal 94, no. 7: 248–255.
    doi: 10.1111/avj.12459google scholar: lookup
  15. McManus JM, Bohn K, Alyamani M, Chung Y‐M, Klein EA, Sharifi N. Rapid and Structure‐Specific Cellular Uptake of Selected Steroids. PLoS One 14, no. 10: e0224081.
    doi: 10.1371/journal.pone.0224081google scholar: lookup
  16. McRobb L, Handelsman DJ, Kazlauskas R, Wilkinson S, McLeod MD, Heather AK. Structure–Activity Relationships of Synthetic Progestins in a Yeast‐Based In Vitro Androgen Bioassay. Journal of Steroid Biochemistry and Molecular Biology 110, no. 1: 39–47.
    doi: 10.1016/j.jsbmb.2007.10.008google scholar: lookup
  17. . Label: Regumate ‐ Altrenogest Solution. .
  18. Mills PC, Cross SE. Transdermal Drug Delivery: Basic Principles for the Veterinarian. Veterinary Journal 172, no. 2: 218–233.
    doi: 10.1016/j.tvjl.2005.09.006google scholar: lookup
  19. . PubChem Compound Summary for CID 10041070, Altrenogest. .
  20. Niswender GD, Juengel JL, Silva PJ, Rollyson MK, McIntush EW. Mechanisms Controlling the Function and Life Span of the Corpus Luteum. Physiological Reviews 80, no. 1: 1–29.
    doi: 10.1152/physrev.2000.80.1.1google scholar: lookup
  21. Poet TS, McDougal JN. Skin Absorption and Human Risk Assessment. Chemico‐Biological Interactions 140, no. 1: 19–34.
    doi: 10.1016/s0009-2797(02)00013-3google scholar: lookup
  22. Proctor AR. The Occupational Health Hazards of Altrenogest. .
  23. Riviere JE, Papich MG. Veterinary Pharmacology and Therapeutics. 9th ed..
  24. Roberts MS, Cross SE, Anissimov YG. Factors Affecting the Formation of a Skin Reservoir for Topically Applied Solutes. Skin Pharmacology and Physiology 17, no. 1: 3–16.
    doi: 10.1159/000074057google scholar: lookup
  25. Scheuplein RJ, Blank IH. Permeability of the Skin. Physiological Reviews 51: 702–747.
    doi: 10.1152/physrev.1971.51.4.702google scholar: lookup
  26. Schmook FP, Meingassner JG, Billich A. Comparison of Human Skin or Epidermis Models With Human and Animal Skin in In‐Vitro Percutaneous Absorption. International Journal of Pharmaceutics 215, no. 1: 51–56.
    doi: 10.1016/s0378-5173(00)00665-7google scholar: lookup
  27. Steffey MA, Griffon DJ, Risselada M. A Narrative Review of the Physiology and Health Effects of Burnout Associated With Veterinarian‐Pertinent Occupational Stressors. Frontiers in Veterinary Science 10: 1184525.
    doi: 10.3389/fvets.2023.1184525google scholar: lookup
  28. Steffey MA, Scharf VF, Risselada M. A Narrative Review of Occupational Scheduling That Impacts Fatigue and Recovery Relevant to Veterinarian Well‐Being. Canadian Veterinary Journal 64, no. 7: 674–683.
  29. Talukdar AH, Calhoun ML, Stinson AW. Microscopic Anatomy of the Skin of the Horse. American Journal of Veterinary Research 33, no. 12: 2365–2390.
  30. Tong L, Stewart M, Johnson I. A Comparative Neuro‐Histological Assessment of Gluteal Skin Thickness and Cutaneous Nociceptor Distribution in Horses and Humans. Animals 10, no. 11: 2094.
    doi: 10.3390/ani10112094google scholar: lookup
  31. Travison TG, Morley JE, Araujo AB, O'Donnell AB, McKinlay JB. The Relationship Between Libido and Testosterone Levels in Aging Men. Journal of Clinical Endocrinology and Metabolism 2006;91(7):2509–2513.
    doi: 10.1210/jc.2005-2508google scholar: lookup
  32. U.S. Food and Drug Administration. Potential Health Risks to People Exposed to Altrenogest Products for Horses or Pigs. 2023.
  33. Volkering ME. Variation of Skin Thickness Over the Equine Body and the Correlation Between Skin Fold Measurement and Actual Skin Thickness. 2009.

Citations

This article has been cited 0 times.
Subscribe to our newsletter
Join 99,911 horse owners like you who receive our email updates on horse health and nutrition.