Compounded oral doxycycline in late-term pregnant mares: pharmacokinetics, fetoplacental diffusion, and neonatal safety

Doxycycline is widely used in equine medicine, yet data on its pharmacokinetics and safety during late gestation are scarce. We investigated the pharmacokinetics, fetoplacental diffusion, and safety of compounded oral doxycycline in late-term pregnant mares. In the first experiment, six mares at 300 days of gestation received a single oral dose (10 mg/kg), and plasma concentrations were measured using LC – MS/MS. Pharmacokinetic analysis using non-compartmental and compartmental models showed rapid absorption, with a mean Cmax of about 6000 ng/mL reached within 0.8 h and a terminal half-life of 8.4 h. In the second experiment, seven mares received doxycycline (10 mg/kg, q12 h, orally) from 320 days of gestation until foaling, while six gestational-age-matched mares served as controls. Doxycycline was detected in fetal fluids, neonatal plasma, and synovial fluid, confirming its ability to cross the fetoplacental barrier, albeit at lower concentrations than in maternal plasma. Serial clinical examinations, complete blood counts, and blood chemistry analyses indicated no adverse effects in either mares or foals. Overall, compounded oral doxycycline was well absorbed during late gestation, safely diffused to the fetoplacental unit, and did not compromise maternal or neonatal health at the dose used herein. These findings provide baseline evidence supporting the use of doxycycline in late pregnant mares.