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

Research Overview

• This study examined the pharmacokinetics, fetoplacental transfer, and safety of orally administered compounded doxycycline in mares during late pregnancy.
• The objective was to assess how the drug is absorbed and distributed in pregnant mares and their foals, as well as to evaluate any potential health risks to both mother and offspring.

Background and Rationale

• Doxycycline is a commonly used antibiotic in equine medicine, but detailed data on its behavior and safety during the late stages of pregnancy in mares is lacking.
• Understanding pharmacokinetics (how the drug moves through the body), fetoplacental diffusion (transfer from mare to fetus), and neonatal safety is critical for ensuring effective and safe treatments.

Study Design and Methods

• Two experiments were conducted involving late-term pregnant mares:
• Experiment 1: Six mares, approximately 300 days pregnant, were given a single oral dose of doxycycline at 10 mg/kg.
• Plasma concentrations of doxycycline were measured over time using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
• Pharmacokinetic modeling (both non-compartmental and compartmental) was used to analyze absorption and elimination parameters.
• Experiment 2: Seven mares starting from 320 days gestation received doxycycline orally twice daily (10 mg/kg every 12 hours) until foaling.
• Six similarly aged pregnant mares served as untreated controls to evaluate safety and compare clinical outcomes.

Pharmacokinetic Findings

• Doxycycline was rapidly absorbed following oral administration, achieving a mean peak plasma concentration (Cmax) of approximately 6000 ng/mL within 0.8 hours (Tmax).
• The drug exhibited a terminal half-life of about 8.4 hours, indicating the time it takes for plasma concentration to decrease by half during the elimination phase.

Fetoplacental Transfer

• Doxycycline was detected in fetal fluids, neonatal plasma, and synovial fluid, confirming that the drug crosses the placental barrier to reach the fetus.
• Although fetal and neonatal concentrations were lower than those in the mares’ plasma, the presence in these compartments suggests potential efficacy and exposure to the developing foal.

Safety Assessment

• Repeated clinical examinations along with blood tests, including complete blood counts and blood chemistry panels, were performed on both mares and foals.
• No adverse effects or signs of toxicity were observed in either the pregnant mares or their newborn foals at the administered dose and dosing schedule.

Conclusions and Implications

• Compounded oral doxycycline is effectively absorbed when administered during late pregnancy in mares and achieves plasma levels consistent with therapeutic use.
• The ability of doxycycline to cross the fetoplacental barrier without causing harm to either the mare or foal supports its safe use in late gestation.
• These findings provide important baseline data to inform veterinary clinicians on the dosing, safety, and expected pharmacokinetics of doxycycline in late-term pregnant mares.
• Further research could explore long-term neonatal outcomes and efficacy against specific infections in this population.