title: Pharmacokinetics and tissue distribution of doxycycline after oral administration of single and multiple doses in horses.
abstract: 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.
  
  
  METHODS
  6 adult horses.
  
  
  METHODS
  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 microg/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 17.27 +/- 8.98 times as great in PMNLs, compared with plasma. Drug was detected in aqueous humor at 7.5% to 10% of plasma concentrations. One horse developed signs of acute colitis and required euthanasia.
  
  
  CONCLUSIONS
  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 < or = 0.25 microg/mL. For bacteria with minimum inhibitory concentration of 0.5 to 1.0 microg/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.
authors.affiliation: Clinical Pharmacology, Research Laboratories, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Davis
authors.forename: Jacklyn H
authors.initials: JH
authors.lastname: Salmon
authors.forename: Mark G
authors.initials: MG
authors.lastname: Papich
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004318:Doxycycline / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D005260:Female; D005508:Food Deprivation; D006207:Half-Life; D006736:Horses / Q000378:metabolism*; D008297:Male; D014018:Tissue Distribution
chemical_list: D000900:Anti-Bacterial Agents; D004318:Doxycycline