Pharmacokinetics of Intrarectal Altrenogest in Horses

Abstract

Hospitalized pregnant mares being held nil per os (PO) because of medical or surgical events present a dilemma for pregnancy maintenance therapy, which commonly includes oral altrenogest. Rectal administration of medications is a recognized route for achieving systemic concentrations, but there are no data on the pharmacokinetics of rectal altrenogest administration in horses. The purpose of this study was to determine the pharmacokinetics of altrenogest following PO or per rectum (PR) administration in mares. Using a randomized two-way crossover study design, six horses received altrenogest (0.088 mg/kg; PO or PR q 24 hours for 5 days), with a 7-day washout period, and the concentrations of altrenogest were determined by an ultrahigh performance liquid chromatography with tandem mass spectrometry. Plasma concentrations persisted above presumed therapeutic concentrations for a mean of 36 hours (range 24-72 hours) and 5.5 hours (range 3-8 hours) for PO and PR administration, respectively. The calculated half-life (T ½) of PO administration (7.01 ± 3.13 hours) was correspondingly increased when compared to PR administration (2.82 ± 1.07 hours). Relative bioavailability of altrenogest following PR administration was only 5.47%. Altrenogest is rapidly absorbed following PR administration in the horse and reaches therapeutic concentrations, making this a viable method of treatment in NPO mares. The decreased bioavailability and shorter detection time suggest 0.088 mg/kg PR q 4-8 hours would be necessary to maintain therapeutic concentrations over a 24-hour period.

Keywords: Altrenogest; Horse; Intrarectal administration; Pharmacokinetics.