Pharmacokinetics of single intravenous and single and multiple dose oral administration of rifampin in mares.

This article discusses a study on the pharmacokinetics of rifampin, a strong antibiotic, in horses. The study examines the drug’s behavior after a single intravenous infusion, a single oral dose, and multiple oral doses and confirms the current dosage recommendation for common, harmful bacteria.

Study Design

• The researchers designed the study to assess the disposition of rifampin in six healthy mares. They chose to administer the antibiotic either through single intravenous (directly into the bloodstream) or oral doses, as well as multiple oral doses, at a concentration of 10 mg/kg twice daily.
• The team used a high-performance liquid chromatographic (HPLC) method to gauge the pharmacokinetic variables of rifampin. This was to ensure their findings could be comparable to past studies that used a microbiological assay.

Key Findings

• A notable finding concerned rifampin’s major metabolite, desacetylrifampin. Although no trace of this metabolite appeared in the serum, researchers found it present in low concentrations in the urine.
• The study found that the average trough concentrations of rifampin significantly rose from the first to the second dose of the multi-dose oral test, and then remained stable for up to 72 hours.
• Concentration levels of rifampin significantly dropped at the 84-hour mark, which coincidentally marks 12 hours following the final dose, indicating the drug’s half-life in the body decreases over time.
• The team discovered that rifampin had a relatively high binding rate with the serum protein (about 78%) in the concentration range between 2-20 micrograms/ml.
• The average trough serum concentrations of ‘unbound’ or ‘free’ rifampin (not bound to proteins) ranged from 0.67 micrograms/ml at 24 hours, to 0.40 micrograms/ml at the 72-hour point. At 84 hours, the mean unbound serum rifampin concentration lowered to 0.30 micrograms/ml.
• These concentrations exceeded the minimum inhibitory concentration (MIC) for most Gram-positive bacterial isolates from horses. MIC is the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation.

Implications and Recommendations

• The researchers conclude their findings by agreeing with the existing recommended dosage for rifampin, which is 10 mg/kg administered orally twice a day. This dosage will render most streptococci, Rhodococcus equi, and coagulase-positive staphylococci susceptible to the drug, making it an effective choice of treatment for these bacteria in horses.