Antimicrobial disposition in pulmonary epithelial lining fluid of horses, part II. Doxycycline.
Abstract: Doxycycline concentrations, following two types of oral administration to horses, in pulmonary epithelial lining fluid (PELF) were examined and compared to plasma concentrations. The oral bioavailability was estimated from plasma concentrations achieved after an intravenous study in two horses. Doxycycline (10 mg/kg) was administered either intragastric or as topdressing to nonfasted horses. Blood samples were collected for drug analysis, before and 11 times after administration during 24 h. PELF samples were collected by a tampon device four times after drug administration and analysed for doxycycline concentrations. Another two horses received doxycycline intravenously at a dose of 3 mg/kg and plasma was taken 14 times during a 24- h period. The oral bioavailability of doxycycline was calculated to 17% after intragastric administration and 6% after topdressing administration in nonfasted horses. The degree of penetration of doxycycline into PELF, as described by AUC(PELF) /AUC(plasma) ratios, was 0.87 after intragastric administration. The results indicate that clinically relevant doxycycline concentrations are possible to maintain in PELF after intragastric administration. Furthermore, if bioavailability could be enhanced for per os administration, doxycycline might be a valuable drug for the treatment of lower airway infections in horses.
© 2010 Blackwell Publishing Ltd.
Publication Date: 2010-08-24 PubMed ID: 20950348DOI: 10.1111/j.1365-2885.2010.01229.xGoogle Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study evaluates how the drug doxycycline is absorbed and distributed in horses, particularly in the lung fluid, when given orally. It suggests that doxycycline might be effective for treating lower respiratory infections in horses if its absorption could be improved.
Methodology
- The study investigates the absorption and concentration of doxycycline in horse’s pulmonary epithelial lining fluid (PELF) following two types of oral administration.
- Doxycycline dosage of 10 mg/kg was administered either directly into the stomach or as a food supplement to nonfasted horses.
- Blood samples were collected from the horses before and several times after the drug administration.
- Further samples of PELF were collected using a tampon device.
- All the collected samples were analyzed for doxycycline concentrations.
- The same procedure was then carried out in the case of intravenous administration of doxycycline at a dose of 3 mg/kg.
Findings
- The study found that oral absorption, or bioavailability, of doxycycline was significantly lower than when administered intravenously.
- Specifically, bioavailability was found to be 17% after direct administration into the stomach and dropped to 6% when administered with food.
- The degree to which doxycycline penetrates into PELF, as measured by the AUC(PELF)/AUC(plasma) ratios, was found to be 0.87 after gastric administration.
- This indicates that even though oral bioavailability is low, relevant concentrations of doxycycline can still be maintained in PELF following direct stomach administration.
Conclusion
- This research suggests that, despite its low oral absorption, doxycycline could still be a valuable medicine for treating lower airway infections in horses.
- However, the efficiency of the treatment is likely to be enhanced if the bioavailability of doxycycline could be improved for oral administration.
Cite This Article
APA
Winther L, Honoré Hansen S, Baptiste KE, Friis C.
(2010).
Antimicrobial disposition in pulmonary epithelial lining fluid of horses, part II. Doxycycline.
J Vet Pharmacol Ther, 34(3), 285-289.
https://doi.org/10.1111/j.1365-2885.2010.01229.x Publication
Researcher Affiliations
- Department of Large Animal Sciences, Faculty of Life Sciences, University of Copenhagen, Taastrup, Denmark. low@dkma.dk
MeSH Terms
- Administration, Oral
- Animals
- Anti-Bacterial Agents / administration & dosage
- Anti-Bacterial Agents / pharmacokinetics
- Biological Availability
- Bronchoalveolar Lavage Fluid / chemistry
- Chromatography, High Pressure Liquid / veterinary
- Doxycycline / administration & dosage
- Doxycycline / pharmacokinetics
- Drug Administration Schedule / veterinary
- Escherichia coli / drug effects
- Female
- Horses
- Injections, Intravenous / veterinary
- Mass Spectrometry / veterinary
- Microbial Sensitivity Tests / veterinary
- Pasteurella / drug effects
- Respiratory Mucosa / metabolism
- Staphylococcus aureus / drug effects
- Streptococcus equi / drug effects
Citations
This article has been cited 6 times.- Koutsoumanis K, Allende A, Alvarez-Ordóñez A, Bolton D, Bover-Cid S, Chemaly M, Davies R, De Cesare A, Herman L, Hilbert F, Lindqvist R, Nauta M, Ru G, Simmons M, Skandamis P, Suffredini E, Andersson DI, Bampidis V, Bengtsson-Palme J, Bouchard D, Ferran A, Kouba M, López Puente S, López-Alonso M, Nielsen SS, Pechová A, Petkova M, Girault S, Broglia A, Guerra B, Innocenti ML, Liébana E, López-Gálvez G, Manini P, Stella P, Peixe L. Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 12: Tetracyclines: tetracycline, chlortetracycline, oxytetracycline, and doxycycline. EFSA J 2021 Oct;19(10):e06864.
- Drwiega EN, Rodvold KA. Penetration of Antibacterial Agents into Pulmonary Epithelial Lining Fluid: An Update. Clin Pharmacokinet 2022 Jan;61(1):17-46.
- 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).
- Rhodes DM, Magdesian KG, Byrne BA, Kass PH, Edman J, Spier SJ. Minimum inhibitory concentrations of equine Corynebacterium pseudotuberculosis isolates (1996-2012). J Vet Intern Med 2015 Jan;29(1):327-32.
- 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.
- Rodvold KA, George JM, Yoo L. Penetration of anti-infective agents into pulmonary epithelial lining fluid: focus on antibacterial agents. Clin Pharmacokinet 2011 Oct;50(10):637-64.
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