Study of intragastric administration of doxycycline: pharmacokinetics including body fluid, endometrial and minimum inhibitory concentrations.
Authors: Bryant J E, Brown M P, Gronwall R R, Merritt K A
Journal: Equine veterinary journal
Summary
# Editorial Summary: Oral Doxycycline Pharmacokinetics in Mares Bryant and colleagues investigated whether intragastric doxycycline achieves therapeutic concentrations in equine serum, body cavities and tissues, and determined the antibiotic susceptibility of common equine pathogens to guide clinical dosing recommendations. Using a two-stage approach, they administered doxycycline hyclate to mares either as a single 3 mg/kg dose or as repeated 10 mg/kg doses every 12 hours via nasogastric tube, measuring drug concentrations in blood, synovial fluid, peritoneal fluid, urine, endometrial tissue and cerebrospinal fluid over time. The repeated 10 mg/kg dosing regimen achieved mean peak serum concentrations of 0.42 µg/ml by the fifth dose with therapeutic trough levels exceeding 0.16 µg/ml, whilst synovial and peritoneal fluid concentrations reached approximately 0.46 and 0.43 µg/ml respectively—notably, endometrial tissue accumulated doxycycline to 1.30 µg/ml, though CSF penetration was negligible. Critically, *Staphylococcus aureus* isolates showed an MIC₉₀ of 0.25 µg/ml and *Streptococcus zooepidemicus* of ≤1.0 µg/ml, meaning the achieved concentrations should overcome susceptible gram-positive infections in joint and peritoneal spaces, as well as reproductive tract infections. For practitioners, this evidence supports 10 mg/kg oral doxycycline every 12 hours for susceptible infections in these locations, though the poor CNS penet
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Practical Takeaways
- •Doxycycline at 10 mg/kg orally every 12 hours is suitable for treating gram-positive infections (particularly Streptococcus and Staphylococcus) in horses, achieving adequate serum and tissue concentrations above MIC for susceptible organisms
- •This dosing regimen achieves good penetration into synovial and peritoneal fluids, making it useful for joint and abdominal infections, though CNS penetration is poor so it is not suitable for neurological infections
- •Practitioners should confirm bacterial susceptibility with culture and sensitivity testing, targeting organisms with MIC ≤0.25 µg/ml for optimal therapeutic outcomes
Key Findings
- •Intragastric doxycycline at 10 mg/kg every 12 hours achieved peak serum concentrations of 0.42 ± 0.05 µg/ml after the fifth dose with trough concentrations >0.16 µg/ml
- •Drug penetrated synovial (0.46 ± 0.13 µg/ml), peritoneal (0.43 ± 0.07 µg/ml), and endometrial tissues (1.30 ± 0.36 µg/ml) but was not detected in cerebrospinal fluid
- •MIC90 for Streptococcus zooepidemicus was ≤1.0 µg/ml and for Staphylococcus aureus was 0.25 µg/ml across 168 equine bacterial isolates
- •Doxycycline half-life was 8.7 ± 1.6 hours with volume of distribution of 25.3 ± 5.0 l/kg, supporting 12-hour dosing intervals