Pharmacokinetics of Intrarectal Altrenogest in Horses.

The research article explores the pharmacokinetics of orally and rectally administrated altrenogest in mares. The study reveals that rectal administration of altrenogest is a possible way of treatment in horses that can’t receive oral medicine, despite its relative bioavailability being significantly lower compared to oral administration.

Objectives of The Study

• The study primarily aims to determine the pharmacokinetics of altrenogest – a synthetic progestogen employed in maintaining pregnancy in mares, when it is administered orally or rectally.
• The research was triggered by a clinical necessity to administer pregnancy maintenance therapy to hospitalized pregnant mares who cannot eat (nil per dos) due to medical or surgical conditions.
• While rectal administration route has been recognized for achieving systemic drug concentrations, no prior data existed about the pharmacokinetics of rectal altrenogest administration in horses. This study fills that gap.

Research Methodology

• The research adopted a randomized two-way crossover study design involving six horses that received altrenogest either orally or rectally once every 24 hours for 5 days. This was followed by a 7-day washout period.
• The concentrations of altrenogest were traced using an ultrahigh-performance liquid chromatography with tandem mass spectrometry method.

Key Findings

• Rectal administration of altrenogest in horses resulted in a rapid absorption and reached therapeutic concentrations, indicating its feasibility as a treatment method for pregnant mares unable to eat.
• However, the relative bioavailability – the amount of administered drug that reaches the circulating blood and can therefore produce its effects, was very low for rectal administration (only 5.47%) compared to oral administration.
• Furthermore, the calculated half-life (time taken for the level of the drug in the body to reduce by half) for rectal administration was shorter (2.82 ± 1.07 hours) in comparison to oral administration (7.01 ± 3.13 hours).
• This suggests that to maintain therapeutic concentrations over a 24-hour period, a dose of 0.088 mg/kg would need to be administrated rectally every 4-8 hours.

Implication and Future Research

• Despite the lower bioavailability and shorter duration, rectal administration of altrenogest in horses manages to reach therapeutic concentrations, making rectal administration a viable alternative method when oral administration is not possible.
• Future studies are needed to further explore the efficacy and implications of this alternative route of administration, and find ways to maximize the absorption and prolongation of the drug in the system.