Pharmacokinetics and tissue distribution of doxycycline after oral administration of single and multiple doses in horses

Objective-To determine pharmacokinetics, safety, and penetration into interstitial fluid (ISF), polymorphonuclear leukocytes (PMNLs), and aqueous humor of doxycycline after oral administration of single and multiple doses in horses. Animals-6 adult horses. Procedure-The effect of feeding on drug absorption was determined. Plasma samples were obtained after administration of single or multiple doses of doxycycline (20 mg/kg) via nasogastric tube. Additionally, ISF, PMNLs, and aqueous humor samples were obtained after the final administration. Horses were monitored for adverse reactions. Results-Feeding decreased drug absorption. After multiple doses, mean +/- SD time to maximum concentration was 1.63 +/- 1.36 hours, maximum concentration was 1.74 +/- 0.3 mu g/mL, and elimination half-life was 12.07 +/- 3.17 hours. Plasma protein binding was 81.76 +/- 2.43%. The ISF concentrations correlated with the calculated percentage of non-protein-bound drug. Maximum concentration was 1727 +/- 8.98 times as great in PMNLs, compared with plasma. Drug was detected in aqueous humor at 75% to 10% of plasma concentrations. One horse developed signs of acute colitis and required euthanasia. Conclusions and Clinical Relevance-Results suggest that doxycycline administered at a dosage of 20 mg/kg, PO, every 24 hours will result in drug concentrations adequate for killing intracellular bacteria and bacteria with minimum inhibitory concentration <= 0.25 mu g/mL. For bacteria with minimum inhibitory concentration of 0.5 to 1.0 mu g/mL, a dosage of 20 mg/kg, PO, every 12 hours may be required; extreme caution should be exercised with the higher dosage until more safety data are available.