Nonlinear Mixed-Effect Pharmacokinetic Modeling and Distribution of Doxycycline in Healthy Female Donkeys after Multiple Intragastric Dosing-Preliminary Investigation.
Authors: Chapuis Ronan J J, Smith Joe S, French Hilari M, Toka Felix Ngosa, Peterson Erik W, Little Erika L
Journal: Animals : an open access journal from MDPI
Summary
# Editorial Summary: Doxycycline Pharmacokinetics in Donkeys Doxycycline is widely used in equine practice for bacterial infections, yet donkeys—with their distinct metabolic pathways—may handle this antibiotic quite differently from horses, a gap that has received little investigation until now. Researchers administered five sequential oral doses of doxycycline hyclate (10 mg/kg every 12 hours) to eight healthy female donkeys via nasogastric tube, then measured drug concentrations in serum, urine, synovial fluid and endometrial tissue over 72 hours using competitive enzyme immunoassay, fitting the data to a nonlinear mixed-effects model. The drug followed a one-compartment kinetic profile with first-order absorption and linear elimination, characterised by unusually high volume of distribution (108 L/kg) and rapid absorption rate (10.3 h⁻¹), yet serum and tissue concentrations remained below the minimum inhibitory concentrations established for common equine pathogens at the tested dosage. These findings suggest that standard equine doxycycline protocols are inadequate in donkeys and may result in subtherapeutic exposure, with significant implications for treatment efficacy and antimicrobial stewardship; further dose-ranging studies are essential to establish appropriate regimens for donkey patients.
Read the full abstract on PubMed
Practical Takeaways
- •Current oral doxycycline dosing protocols established for horses (10 mg/kg q12h) are inadequate for donkeys and will not achieve therapeutic drug levels for treating bacterial infections
- •Veterinarians treating donkey infections should not extrapolate equine antimicrobial dosing to donkeys without species-specific pharmacokinetic data, as donkey metabolism differs significantly
- •Further research is urgently needed to establish appropriate doxycycline doses and dosing intervals specifically for donkeys before this antibiotic can be reliably used in this species
Key Findings
- •Doxycycline in donkeys demonstrated a one-compartment model with linear elimination and first-order absorption after intragastric administration
- •Doxycycline had a high volume of distribution (108 L/kg) and high absorption rate (10.3 h⁻¹) in donkeys compared to horses
- •Oral doxycycline at 10 mg/kg q12h did not achieve therapeutic concentrations in serum, urine, synovial fluid, or endometrium when compared to minimum inhibitory concentrations of common equine pathogens
- •The pharmacokinetics of doxycycline in donkeys differs substantially from horses, indicating species-specific dosing requirements are necessary