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Irish veterinary journal2019; 72; 5; doi: 10.1186/s13620-019-0143-7

Tamoxifen in horses: pharmacokinetics and safety study.

Abstract: Tamoxifen (TAM), a selective modulator of estrogen receptors (SERMs) has been recently explored as a therapeutic option for the oral treatment of airway inflammation in the horse. The objective of this work was to establish pharmacokinetic parameters of TAM and its main metabolites in equines, as well as to determine its clinical safety in short-term treatments. Results: We determined TAM and its three main metabolites (4-OH tamoxifen, endoxifen, and N-desmethyl tamoxifen) in plasma after single administration of 0.25 mg/kg in healthy adult horses ( = 12). A maximum concentration of TAM was achieved 3 h after the oral administration (4.65 pg/mL ± 1.69); 4-OH tamoxifen was the metabolite that reached the highest concentration (78 pg/mL ± 70), followed by N-desmethyl tamoxifen (0.43 pg / mL ± 0.48), and finally endoxifen (0.17 pg/mL ± 0.17). All metabolites showed peak concentration 2 h after oral administration of the drug. Oral TAM bioavailability was 13,15% ± 4,18, with a steady state volume of distribution of 7831 ± 2922 (L/kg). Elimination half-life was 15.40 ± 5.80 h, and clearance was 5876 ± 699 (mL/kg/min). Clinical safety of TAM was determined over a 7-day course of treatment (0.25 mg/kg, orally q 24 h,  = 20). No adverse effects were observed through clinical examination, blood hematology, serum biochemistry, ophthalmological and reproductive examinations. Endometrial edema observed in some mares was attributed to normal cyclic activity. Conclusions: Tamoxifen has moderate oral bioavailability and a large volume of distribution, with three main metabolites in horses. Additionally, oral TAM administration over a 7-day treatment period demonstrated to be clinically safe, without adverse effects on clinical, hematological or serum biochemical parameters. These data could contribute to the continued research into this drug's potential for the treatment of different inflammatory conditions in equine species.
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Publication Date: 2019-06-20 PubMed ID: 31249663PubMed Central: PMC6587269DOI: 10.1186/s13620-019-0143-7Google Scholar: Lookup
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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.

The research article discusses a study about the use of Tamoxifen (TAM), a medicine that modulates estrogen receptors, in horses to treat airway inflammation. The study sought to establish how this drug is absorbed, distributed, metabolized, and excreted in horses, as well as its safety for short-term use.

Research Design and Objectives

  • The primary goal of the study was to determine the pharmacokinetic parameters (how the body affects a drug) of Tamoxifen and its major metabolites in horses.
  • Another objective was to evaluate the clinical safety of Tamoxifen during short-term treatments.

Procedure and Results

  • The researchers administered a single dosage of 0.25 mg/kg of TAM to twelve healthy adult horses.
  • They monitored the concentration of TAM and its three main metabolites (4-OH tamoxifen, endoxifen, and N-desmethyl tamoxifen) in the horses’ plasma over time.
  • The metabolite that reached the highest concentration was found to be 4-OH tamoxifen, followed by N-desmethyl tamoxifen, and finally endoxifen, with all peaking 2 hours after administering the drug.
  • The highest concentration of TAM itself was observed 3 hours after administration.
  • The oral bioavailability, or the proportion of the drug that enters the circulation and can have an active effect, was found to be about 13%, suggesting it has a moderate level of availability when administered orally.
  • The volume of TAM distribution, representing the hypothetical volume that the total amount of drug would need to uniformly distribute to produce the observed blood concentration, was quite large.
  • The elimination half-life, which is the time it takes for half of the drug to be eliminated from the body, was about 15.40 hours.
  • The clearance rate, or the volume of blood cleared of the drug per unit time, was also calculated.
  • Additionally, the clinical safety of TAM was evaluated over a 7-day treatment course. No adverse effects were observed in any clinical, hematological, or serum biochemical parameters.

Conclusions

  • Overall, the study found that Tamoxifen has moderate oral bioavailability and a large volume of distribution in horses, with three main metabolites.
  • The drug was found to be safe for short-term use, with no observed adverse effects.
  • The findings from this research can be useful for further studies into Tamoxifen’s potential use in treating various inflammatory conditions in horses.

Cite This Article

APA
Gajardo G, López-Muñoz R, Plaza A, Uberti B, Sarmiento J, Morán G, Henríquez C. (2019). Tamoxifen in horses: pharmacokinetics and safety study. Ir Vet J, 72, 5. https://doi.org/10.1186/s13620-019-0143-7

Publication

Irish veterinary journal
ISSN: 0368-0762
NlmUniqueID: 0100762
Country: Ireland
Language: English
Volume: 72
Pages: 5
PII: 5

Researcher Affiliations

Gajardo, Gonzalo
  • 1Escuela de Graduados, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile.
López-Muñoz, Rodrigo
  • 2Instituto de Farmacología y Morfofisiología, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile.
Plaza, Anita
  • 3Instituto de Medicina, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile.
Uberti, Benjamin
  • 4Instituto de Ciencias Clínicas, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile.
Sarmiento, José
  • 5Instituto de Fisiología, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile.
Morán, Gabriel
  • 2Instituto de Farmacología y Morfofisiología, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile.
Henríquez, Claudio
  • 2Instituto de Farmacología y Morfofisiología, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile.

Conflict of Interest Statement

Competing interestsThe authors declare that they have no competing interests.

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Citations

This article has been cited 2 times.
  1. Salinas C, Barriga K, Albornoz A, Alarcon P, Quiroga J, Uberti B, Sarmiento J, Henriquez C, Ehrenfeld P, Burgos RA, Moran G. Tamoxifen triggers the in vitro release of neutrophil extracellular traps in healthy horses. Front Vet Sci 2022;9:1025249.
    doi: 10.3389/fvets.2022.1025249pubmed: 36686170google scholar: lookup
  2. Rodríguez M, Quiroga J, Cortés B, Morán G, Henríquez C. Effects of tamoxifen on the immune response phenotype in equine peripheral blood mononuclear cells. Front Vet Sci 2024;11:1381162.
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