Pharmacokinetics of Topical Administration of Altrenogest in Mares and Implications for Human Health

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_max) 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.