Pharmacokinetics of Two Formulations of Altrenogest Administered to Mares.
Abstract: Altrenogest is a synthetic progestin that suppresses reproductive behaviours and assists pregnancy maintenance in female horses. Two formulations are available, a 'weekly' intramuscular injection and a daily oral formulation. Altrenogest administration has returned positive swabs for steroids; consequently, using injectable altrenogest in racing mares is prohibited. Oral administration may be permitted in race mares if there is one clear day between dosing and racing. The only pharmacokinetic data available were generated from geldings. Therefore, to assist veterinarians and analysts in determining accurate dosing and detection intervals, pharmacokinetic analysis using mares is required. Blood samples were taken from 10 mares pretreatment to obtain baseline concentrations. Mares were administered altrenogest, either oral (PO; 0.044 mg/kg; daily for 15 days) or intramuscular (IM; 0.3 mg/kg; twice; Days 0 and 7). On the first and last treatment day, blood samples were taken at designated times post dosing. After a 3-week washout, mares received the alternative treatment with sampling repeated. At the initial dose, for IM administration mean (± SD) plasma altrenogest C was 18.0 ± 6.6 ng/mL at 7.9 ± 3.9 h compared with PO dosing 13.2 ± 5.8 ng/mL at 0.8 ± 0.8 h. Plasma C on the final day was significantly higher (p = 0.002 [IM]; p = 0.006 [PO]). At 24 h post final oral treatment, mean (± SD) plasma altrenogest was 1.0 ± 0.8 ng/mL and at 48 h were 0.65 ± 0.5 ng/mL. Plasma concentrations well exceeding this may indicate that the one clear day rule or dosage recommendations have not been adhered to.
© 2024 The Author(s). Drug Testing and Analysis published by John Wiley & Sons Ltd.
Publication Date: 2024-09-22 PubMed ID: 39307175DOI: 10.1002/dta.3796Google Scholar: Lookup
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Summary
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This research article explores the pharmacokinetics or the bodily uptake, distribution, metabolism, and excretion of two different formulations of Altrenogest, a synthetic progestin used to suppress reproductive behaviours and support pregnancy in mares. It systematically compares the effects of administering either a weekly injectable dose or a daily oral formulation of the drug in female horses.
Objectives
- The primary goal of the study was to provide accurate pharmacokinetic data, which can assist veterinarians and analysts in determining appropriate dosing and detection intervals for mare treatment with Altrenogest.
- Previously, such data had been gathered only from geldings (neutered male horses). This study therefore aimed to fill this gap by conducting analysis with mares.
Methodology
- Initial blood samples were taken from 10 mares to establish baseline altrenogest concentrations.
- The mares were subsequently administered orally (0.044mg/kg daily for 15 days) or received an intramuscular injection (0.3mg/kg on days 0 and 7).
- Blood samples were taken at designated times after dosing on the first and last treatment days.
- After a 3-week break, the treatment methods were swapped, and the sampling process was repeated.
Findings
- The researchers found that, on average, the plasma Altrenogest concentrations following an initial intramuscular injection was 18.0±6.6ng/mL, occurring at 7.9±3.9 hours, whereas, it was 13.2±5.8 ng/mL at 0.8±0.8 hours for oral dosage.
- On the final day of treatment, plasma concentrations were significantly higher for both injection (p=0.002) and oral formulation (p=0.006).
- At 24 hours post the final oral treatment, the plasma Altrenogest average concentrations reduced to 1.0±0.8ng/mL, and further dropped to 0.65±0.5 ng/mL after 48 hours.
- The study concludes that if plasma concentrations exceed aforementioned levels, it might indicate non-compliance with the prescribed one clear day rule or dosage recommendations.
Cite This Article
APA
Loy J, Cawley A, Sornalingam K, Scrivener CJ, Keledjian J, Noble GK.
(2024).
Pharmacokinetics of Two Formulations of Altrenogest Administered to Mares.
Drug Test Anal.
https://doi.org/10.1002/dta.3796 Publication
Researcher Affiliations
- School of Agricultural, Environmental and Veterinary Sciences, Charles Sturt University, Wagga Wagga, New South Wales, Australia.
- Racing Analytical Services Limited, Flemington, Victoria, Australia.
- Australian Racing Forensic Laboratory, Racing NSW, Sydney, New South Wales, Australia.
- School of Agricultural, Environmental and Veterinary Sciences, Charles Sturt University, Wagga Wagga, New South Wales, Australia.
- Australian Racing Forensic Laboratory, Racing NSW, Sydney, New South Wales, Australia.
- School of Agricultural, Environmental and Veterinary Sciences, Charles Sturt University, Wagga Wagga, New South Wales, Australia.
Grant Funding
- Agrifutures Australia
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