Pharmacological indices and pulmonary distribution of rifampicin after repeated oral administration in healthy foals.

This research study examines the pharmacokinetics (how the body processes a drug) and pulmonary (lung) distribution of the antibiotic rifampicin in healthy foals (young horses), aimed at improving treatment for equine lung infections caused by Rhodococcus equi.

Study Design

• The research was structured as a controlled, randomised, two-period, crossover, repeated-dose study to assess how the drug rifampicin is processed and distributed in the lungs of healthy foals. This design is typically used to compare different treatments on the same group of subjects.
• The research included an initial phase to measure how rifampicin is distributed after intravenous (i.v.) administration. This helped to establish a baseline understanding of how the drug behaves in the body.
• Two dosage levels (10 mg/kg bwt and 20 mg/kg bwt) of rifampicin were administered orally to foals once a day for 10 days in the crossover study. Crossover studies help eliminate variances that may occur due to differences among individual foals.
• 24 hours after the last oral dosage, lung fluid (ELF) and bronchoalveolar lavage cells (BALC) were sampled using bronchoalveolar lavage, a technique to wash out cells and other components from bronchial and bronchiolar spaces.
• The amount of rifampicin and its metabolite, 25-O-desacetyl rifampicin, were quantified using liquid chromatography tandem-mass spectrometry, a method to separate, identify and quantify compound.

Findings of the Study

• Results highlight that rifampicin, when administered via an intravenous method, had an estimated distribution volume of ~0.85 L/kg and a terminal elimination half-life of ~11 hours.
• When given orally, rifampicin absorption was slow (T , range: 2.5-8.0 hours) and elimination half-lives ranged from ~6-8 hours.
• Concentrations of the drug in lung fluid (ELF) and bronchoalveolar lavage cells (BALC) were measurable 24 hours after the last oral dosage, indicating that the drug reaches the target site within the lung.
• The pharmacological indices (measured as the areas under the plasma concentration time curve, or AUC, divided by the minimum inhibitory concentration, or MIC) were calculated for dosages of 10mg/kg and 20mg/kg, and appear to be effective in combatting less susceptible strains of R.equi.

Conclusions of the Research

• The study did not evaluate the clearance and bioavailability of rifampicin after repeated oral dosing, highlighting an area for further investigation.
• The study suggested that a dosage of 10mg/kg bwt of rifampicin administered once a day is suitable to generate drug concentrations in foals’ lungs above the minimum inhibitory concentration (MIC), the lowest concentration that will inhibit visible growth of a microorganism.
• The authors advocate for future clinical studies to be done using rifampicin in combination with macrolide antibiotics, which have low drug interaction potential, to develop effective treatment plans for R. equi lung infections.