Pharmacokinetics and tissue distribution of doxycycline after oral administration of single and multiple doses in horses.
Abstract: 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.
Publication Date: 2006-02-04 PubMed ID: 16454638DOI: 10.2460/ajvr.67.2.310Google Scholar: Lookup
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- Clinical Trial
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research investigated the pharmacokinetics, safety, and tissue penetration of doxycycline—a commonly used antibiotic—in horses. The study found that feeding decreased drug absorption, and that the drug was able to penetrate certain tissues with varying concentrations. A potential risk was also identified, as one horse developed acute colitis during the study.
Research Methods
- The study involved six adult horses, to whom doxycycline was administered orally through a nasogastric tube.
- Researchers studied both single and multiple doses of doxycycline, measuring the impact of feeding on drug absorption.
- Plasma samples were collected after doxycycline dosage and analyzed.
- Interstitial fluid (ISF), polymorphonuclear leukocytes (PMNLs), and aqueous humor samples were collected after the last dosage to assess the drug’s tissue penetration.
- Horses were continuously monitored for any adverse reactions throughout the study.
Results
- The study found that feeding the horses decreased the absorption of the drug.
- The average time to reach maximum concentration in the blood after multiple doses was approximately 1.63 hours.
- Maximum concentration was 1.74 micrograms per milliliter, and the drug had an average half-life of 12.07 hours.
- Doxycycline was found to bind to plasma proteins at an average rate of 81.76%, and concentrations in the ISF mirrored the calculated percentage of the drug not bound to proteins.
- Drug concentrations were noticeably higher in PMNLs compared to plasma, and was also found in aqueous humor at 7.5 to 10% of plasma concentrations.
- One horse developed acute colitis—a severe inflammation of the colon—and had to be euthanized.
Conclusions and Implications
- The findings suggest that a dosage of 20 mg/kg of doxycycline administered orally every 24 hours would result in drug concentrations sufficient to kill intracellular bacteria and those with a minimum inhibitory concentration (MIC) of 0.25 micrograms per milliliter or less.
- For bacterial strains with an MIC of 0.5 to 1.0 micrograms per milliliter, a higher dosage of 20 mg/kg administered every 12 hours may be necessary.
- However, the study suggests that such a higher dosage should be administered with extreme caution until further safety data can be gathered, given the development of acute colitis in one of the study subjects.
Cite This Article
APA
Davis JL, Salmon JH, Papich MG.
(2006).
Pharmacokinetics and tissue distribution of doxycycline after oral administration of single and multiple doses in horses.
Am J Vet Res, 67(2), 310-316.
https://doi.org/10.2460/ajvr.67.2.310 Publication
Researcher Affiliations
- Clinical Pharmacology, Research Laboratories, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
MeSH Terms
- Administration, Oral
- Animals
- Anti-Bacterial Agents / administration & dosage
- Anti-Bacterial Agents / blood
- Anti-Bacterial Agents / pharmacokinetics
- Area Under Curve
- Doxycycline / administration & dosage
- Doxycycline / blood
- Doxycycline / pharmacokinetics
- Drug Administration Schedule
- Female
- Food Deprivation
- Half-Life
- Horses / metabolism
- Male
- Tissue Distribution
Citations
This article has been cited 18 times.- Liu Z, Jiao X, Xie L, Ren W, Lv L, Du J, Huang X. A high content (30%) stable doxycycline hyclate drinking-water solution for broilers: preparation, stability, and bioequivalence. Front Vet Sci 2025;12:1740059.
- Martínez J, Marín P, Egas DA, Llivi-Marcatoma J, Mira-Naranjo JM, Badillo E, Yuste MT, Escudero E, Galecio JS. Pharmacokinetics of Doxycycline in Alpacas After Intravenous and Subcutaneous Administration. Antibiotics (Basel) 2025 Mar 1;14(3).
- Gilbertie JM, Sheahan BJ, Vaden SL, Jacob ME. Canine urothelial cell model to study intracellular bacterial community development by uropathogenic Escherichia coli. PLoS One 2025;20(1):e0316834.
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- Scala E, van Galen G, Skärlina EM, Durie I. Do post-surgical multiresistant urinary infections occur in horses? Case of unilateral pyelonephritis caused by extended-spectrum beta-lactamase-producing bacteria as a complication of cystotomy. Vet Med Sci 2023 Sep;9(5):2042-2052.
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- Chapuis RJJ, Smith JS, French HM, Toka FN, Peterson EW, Little EL. Nonlinear Mixed-Effect Pharmacokinetic Modeling and Distribution of Doxycycline in Healthy Female Donkeys after Multiple Intragastric Dosing-Preliminary Investigation. Animals (Basel) 2021 Jul 9;11(7).
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- Zozaya H, Gutierrez L, Bernad MJ, Sumano H. Pharmacokinetics of a peroral single dose of two long-acting formulations and an aqueous formulation of doxycycline hyclate in horses. Acta Vet Scand 2013 Mar 8;55(1):21.
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