Penicillin and Gentamicin Concentrations in the Uterine Fluid of Non-Pregnant Mares Following a Single Intrauterine Infusion.

Overview

• This study measured how much penicillin and gentamicin, two common antibiotics, remain in the uterine fluid of mares after a single intrauterine infusion.
• It compared a standard formulation with a long-acting (slow-release) formulation to see which maintained therapeutic antibiotic levels longer.

Background and Purpose

• Equine intrauterine antimicrobials like penicillin and gentamicin are frequently used to treat uterine infections in mares.
• Despite their widespread use, detailed pharmacokinetic data (how the drugs disperse and persist in the uterus) is limited.
• The goal was to quantify antibiotic concentrations over time after infusion with either:
• A standard antibiotic mixture (referred to as PPGent)
• A long-acting, slow-release version (referred to as LA-PPGent)
• The hypothesis was that both would reach therapeutic levels, but the long-acting formulation would maintain effective concentrations for a longer duration.

Methods

• Subjects: 12 non-pregnant mares divided into two groups:
• 6 mares received the standard PPGent formulation
• 6 mares received the LA-PPGent long-acting formulation
• Dosing: Each mare was given a single intrauterine infusion containing 2400 mg of procaine penicillin and 200 mg of gentamicin.
• Sample collection: Uterine fluid was collected intermittently over a 72-hour period post-infusion.
• Analytical methods: Concentrations of both antibiotics in the uterine fluid were measured using:
• High-Performance Liquid Chromatography (HPLC)
• Ultra-High-Performance Liquid Chromatography with Tandem Mass Spectrometry (UHPLC-MS/MS)

Key Findings

• Standard formulation group (PPGent):
• Maximal antibiotic concentration occurred at 0.5 hours post-infusion.
• Penicillin concentration peaked at approximately 10,123 µg/mL (±4298 µg/mL).
• Gentamicin concentration peaked at around 3397 µg/mL (±1338 µg/mL).
• Both antibiotics maintained concentrations above the minimum inhibitory concentration (MIC) for relevant pathogens for the full 72-hour study period.
• Average concentrations at 72 hours were still above MIC: 2.59 µg/mL for penicillin and 2.14 µg/mL for gentamicin.
• Long-acting formulation group (LA-PPGent):
• Achieved significantly lower peak concentrations compared to the standard group:
• Penicillin peak around 2214 µg/mL (±968 µg/mL), with p < 0.05 indicating statistical significance for the difference.
• Gentamicin peak approximately 1859 µg/mL (±2413 µg/mL), showing variable levels.
• These concentrations remained above MIC for a shorter duration than the standard formulation.
• This was unexpected since the long-acting matrix was anticipated to maintain therapeutic levels longer.

Implications

• The standard PPGent intrauterine infusion results in very high local concentrations of penicillin and gentamicin that stay above therapeutic levels for 72 hours.
• The slow-release LA-PPGent formulation, contrary to expectations, produced lower peak concentrations and did not sustain therapeutic antibiotic levels as long.
• Clinically, this suggests that the commonly used standard intrauterine antibiotic infusion may be more effective in maintaining adequate uterine drug levels over time in non-pregnant mares.
• More research may be needed to optimize formulations for prolonged intrauterine antimicrobial therapy.

Summary

• This pharmacokinetic study highlights the actual performance of two intrauterine antibiotic formulations in mares.
• Therapeutic antibiotic concentrations above MICs are crucial for effectively treating uterine infections and preventing bacterial resistance.
• Findings support continued use of the standard penicillin-gentamicin infusion over the long-acting variant, at least under current formulation conditions.