Farmacocinética da progesterona exógena e seus efeitos no trato reprodutor de éguas

Abstract

Progesterone (P4) plays a key role in establishing uterine receptivity for early maintenance ofpregnancy and is widely used pharmacologically in hormonal protocols to prepare recipientmares in embryo transfer programs. Despite its routine use, information regarding thepharmacokinetics of exogenous P4 in acyclic mares remains limited, particularly amongdifferent formulations. The objective of this study was to characterize the pharmacokineticprofile of exogenous injectable P4 administered at two doses (900 mg and 1500 mg) and as avaginal implant (1 g), as well as to evaluate its effects on uterine edema and tone. Serial bloodsamples were collected for P4 quantification by ultra-performance liquid chromatographycoupled with tandem mass spectrometry (UPLC–MS/MS), and pharmacokinetic analysis wasperformed using a non-compartmental model. Daily reproductive tract evaluations wereconducted by ultrasonography and rectal palpation. The 1500 mg dose resulted in a highermaximum plasma concentration and longer systemic persistence, maintaining levels above 2.5ng/mL for more than 216 hours, whereas the 900 mg dose maintained adequate concentrationsfor less than 24 hours. The vaginal implant promoted rapid absorption, maintainingconcentrations close to the minimum threshold for approximately 72 hours. Greater systemicpersistence and prolonged half-life were observed in lighter mares. A progressive reduction inuterine edema and an increase in uterine tone was observed in all treatments, characterizing aprogesterone-influenced uterine environment. In conclusion, the pharmacokinetics ofexogenous P4 in mares are dependent on both formulation and dose. The vaginal implantappears suitable for short-term protocols, whereas the 1500 mg injectable progesteroneformulation is appropriate for prolonged maintenance, although it may impair recipient mareresynchronization.