Abstract: Background – Oral minocycline pharmacokinetic data in horses are lacking, and recommended doses result in lower plasma concentrations when compared to other species, raising concerns about therapeutic failure and antimicrobial resistance. Hypothesis/Objectives – To describe the pharmacokinetics and safety of a high dose of oral minocycline in horses. We hypothesized that a high dose of minocycline would achieve higher steady-state plasma concentrations than conventional doses. Animals – Seven healthy adult horses from a research herd. Methods – Prospective, observational study. Horses were administered minocycline (8 mg/kg PO, q12h) for 5d. Safety was assessed through physical examinations, bloodwork, and evaluation of fecal consistency and appetite. Plasma minocycline concentrations were measured using LC-MS/MS, and commercial software was used for noncompartmental pharmacokinetic analysis. Results – Physical examinations remained unremarkable. All horses exhibited a good to excellent appetite and developed transient, soft-formed feces. Statistical differences were found in mean corpuscular volume, mean platelet volume, and calcium. At steady state, mean ±SD maximum plasma concentration was 1.46±1.36 μg/ml and half-life was 13.60±2.62 h. The average plasma concentration was 0.73±0.67 μg/ml and concentrations at 6h and 12h were 0.96±1.22 and 0.46±0.39 μg/ml, respectively. Volume of distribution/F and clearance/F were 32.20±24.14 L/kg and 1.54±1.07 L/h/kg, respectively. Conclusions and Clinical Importance – A high dose of minocycline appears well tolerated in horses. Based on plasma concentrations, an 8 mg/kg dose of minocycline should target bacteria with MIC values ≤0.25 μg/ml, twice that intended with recommended doses. This would minimize exposure to subtherapeutic concentrations that could promote antimicrobial resistance.
