Pharmacological indices and pulmonary distribution of rifampicin after repeated oral administration in healthy foals.
Authors: Berlin S, Kirschbaum A, Spieckermann L, Oswald S, Keiser M, Grube M, Venner M, Siegmund W
Journal: Equine veterinary journal
Summary
# Rifampicin Pharmacokinetics and Lung Distribution in Foals Rhodococcus equi pneumonia in foals has long been treated with rifampicin based on clinical experience rather than robust pharmacokinetic and pharmacodynamic data, leaving uncertainty about optimal dosing strategies. Researchers administered rifampicin intravenously and orally (at 10 and 20 mg/kg bodyweight once daily for ten days) to six healthy foals, measuring drug concentrations in plasma, epithelial lining fluid (ELF), and bronchoalveolar lavage cells (BALC) using advanced mass spectrometry, whilst confirming rifampicin's enzyme-inducing effects through plasma cholesterol metabolite ratios. At the standard 10 mg/kg dose, lung tissue concentrations reached 1.01 µg/mL in ELF and 1.25 µg/mL in BALC—sufficient to exceed the MIC₉₀ (0.5 µg/mL) for less susceptible R. equi strains, with an AUC₀₋₂₄h:MIC ratio of 145 hours, whilst doubling the dose to 20 mg/kg achieved ratios of 322 hours. These findings validate 10 mg/kg once-daily dosing as pharmacodynamically appropriate for foal lung infections, though practitioners should note that oral rifampicin absorption is variable (peak concentrations occurring 2.5–8 hours post-dosing) and that future clinical trials combining rifampicin with macrolides are needed to establish definitive treatment protocols and account for potential drug interactions in clinical practice.
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Practical Takeaways
- •Rifampicin 10 mg/kg once daily orally achieves therapeutic lung concentrations suitable for treating R. equi pneumonia in foals, supporting current empirical dosing protocols
- •The slow and variable oral absorption (2.5-8.0 h Tmax) and moderate half-life (6-8 h) mean consistent once-daily dosing is important; avoid assuming peak concentrations are reached quickly after administration
- •Rifampicin induces cytochrome P450 enzymes, so be cautious when co-administering with other drugs (especially macrolide antibiotics commonly used with rifampicin); monitor for reduced efficacy of concurrent medications and plan clinical combinations carefully
Key Findings
- •Rifampicin at 10 mg/kg once daily achieved lung concentrations (ELF 1.01 μg/mL, BALC 1.25 μg/mL) above MIC90 for R. equi (0.5 μg/mL)
- •Oral rifampicin was slowly absorbed (Tmax 2.5-8.0 h) with apparent half-lives of 6-8 h after repeated dosing
- •AUC0-24h/MIC ratios of 145 h (10 mg/kg) and 322 h (20 mg/kg) suggest adequate PK/PD target attainment for R. equi treatment
- •Enzyme induction by rifampicin was confirmed, indicating potential for drug interactions with other medications