Study of intragastric administration of doxycycline: pharmacokinetics including body fluid, endometrial and minimum inhibitory concentrations.
Abstract: The objectives of this study were to determine the pharmacokinetics and tissue concentrations of doxycycline after repeated intragastric administration, and to determine the minimum inhibitory concentrations (MIC) for equine pathogenic bacteria. In experiment 1, 2 mares received a single intragastric dose of doxycycline hyclate (3 mg/kg bwt). Mean peak serum concentration was 0.22 microg/ml 1 h postadministration. In experiment 2, 5 doses of doxycycline hyclate (10 mg/kg bwt), dissolved in water, were administered to each of 6 mares via nasogastric tube at 12 h intervals. The mean +/- s.e. peak serum doxycycline concentration was 0.32+/-0.16 microg/ml 1 h after the first dose and 0.42+/-0.05 microg/ml 2 h after the fifth dose. The mean trough serum concentrations were > 0.16 microg/ml. Highest mean synovial concentration was 0.46+/-0.13 microg/ml and highest mean peritoneal concentration was 0.43+/-0.07 microg/ml, both 2 h after the fifth dose. Highest urine concentration was mean +/- s.e. 145+/-25.4 microg/ml 2 h after the last dose. Highest endometrial concentration was mean +/- s.e. 1.30+/-0.36 microg/ml 3 h after the fifth dose. Doxycycline was not detected in any of the CSF samples. Mean +/- s.e. Vd(area) was 25.3+/-5.0 l/kg and mean t1/2 was 8.7+/-1.6 h. In experiment 3, minimum inhibitory concentrations of doxycycline were determined for 168 equine bacterial culture specimens. The MIC90 was < or = 1.0 microg/ml for Streptococcus zooepidemicus and 0.25 microg/ml for Staphylococcus aureus. Based on drug concentrations achieved in the serum, synovial and peritoneal fluids and endometrial tissues and MIC values determined in the present study, doxycycline at a dose of 10 mg/kg bwt per os every 12 h may be appropriate for the treatment of infections caused by susceptible (MIC < 0.25 microg/ml) gram-positive organisms in horses.
Publication Date: 2000-06-03 PubMed ID: 10836479DOI: 10.2746/042516400776563608Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research paper focuses on the analysis of how the body absorbs, distributes, metabolizes and expels ‘doxycycline’, a type of antibiotic, when administered through the stomach, followed by establishing the minimum concentration of this drug required to suppress harmful bacteria in horses.
Objective of the Study
- The aim of this study is to understand the pharmacokinetics or the movement of doxycycline through the body after it is given through the stomach.
- The researchers also want to find the smallest amount of doxycycline required to inhibit certain bacteria that cause diseases in horses.
Methodology
- Two experiments were conducted, involving the intragastric administration of doxycycline. The first involved two horses receiving a single dose, while the second involved six horses receiving five doses at regular intervals.
- The researchers then measured the serum, synovial, peritoneal, urine, and endometrial concentration of doxycycline at various time intervals.
Results
- Following a single dose, peak serum concentration was observed after 1 hour, and with repeated doses, it was observed after two hours of the last dose.
- Both synovial and peritoneal fluids showed maximum concentration two hours after the last dose.
- The highest concentration was found in urine and endometrial tissues two and three hours after the last dose, respectively. However, doxycycline was not detected in any of the cerebrospinal fluid samples.
Testing Inhibitory Concentrations
- A third experiment involved testing minimum inhibitory concentrations (MICs) of doxycycline on 168 equine bacterial samples.
- The outcome demonstrated that the MICs for specific harmful bacteria (such as Streptococcus zooepidemicus and Staphylococcus aureus) were smaller than or equal to the concentrations achieved in the serum, synovial and peritoneal fluids, and endometrial tissues.
Conclusion
- Based on the drug concentrations achieved and the MIC values determined, the researchers believe that a particular concentration of doxycycline may be suitable in treating infections caused by these specific bacteria in horses.
Cite This Article
APA
Bryant JE, Brown MP, Gronwall RR, Merritt KA.
(2000).
Study of intragastric administration of doxycycline: pharmacokinetics including body fluid, endometrial and minimum inhibitory concentrations.
Equine Vet J, 32(3), 233-238.
https://doi.org/10.2746/042516400776563608 Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, USA.
MeSH Terms
- Animals
- Anti-Bacterial Agents / blood
- Anti-Bacterial Agents / cerebrospinal fluid
- Anti-Bacterial Agents / pharmacokinetics
- Anti-Bacterial Agents / urine
- Area Under Curve
- Ascitic Fluid / chemistry
- Ascitic Fluid / veterinary
- Biopsy / veterinary
- Doxycycline / blood
- Doxycycline / cerebrospinal fluid
- Doxycycline / pharmacokinetics
- Doxycycline / urine
- Endometrium / chemistry
- Female
- Gram-Negative Bacteria / drug effects
- Gram-Negative Bacterial Infections / drug therapy
- Gram-Negative Bacterial Infections / veterinary
- Gram-Positive Bacteria / drug effects
- Gram-Positive Bacterial Infections / drug therapy
- Gram-Positive Bacterial Infections / veterinary
- Half-Life
- Horses / blood
- Horses / cerebrospinal fluid
- Horses / metabolism
- Horses / urine
- Intubation, Gastrointestinal / veterinary
- Microbial Sensitivity Tests
- Pilot Projects
- Synovial Fluid / chemistry
Citations
This article has been cited 7 times.- Chen CJ, Gillett A, Booth R, Kimble B, Govendir M. Pharmacokinetic Profile of Doxycycline in Koala Plasma after Weekly Subcutaneous Injections for the Treatment of Chlamydiosis. Animals (Basel) 2022 Jan 20;12(3).
- 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).
- Erol E, Scortti M, Fortner J, Patel M, Vázquez-Boland JA. Antimicrobial Resistance Spectrum Conferred by pRErm46 of Emerging Macrolide (Multidrug)-Resistant Rhodococcus equi. J Clin Microbiol 2021 Sep 20;59(10):e0114921.
- Divers TJ, Gardner RB, Madigan JE, Witonsky SG, Bertone JJ, Swinebroad EL, Schutzer SE, Johnson AL. Borrelia burgdorferi Infection and Lyme Disease in North American Horses: A Consensus Statement. J Vet Intern Med 2018 Mar;32(2):617-632.
- Caol S, Divers T, Crisman M, Chang YF. In vitro susceptibility of Borrelia burgdorferi isolates to three antibiotics commonly used for treating equine Lyme disease. BMC Vet Res 2017 Sep 29;13(1):293.
- 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.
- Abu-Basha EA, Idkaidek NM, Hantash TM. Pharmacokinetics and bioavailability of doxycycline in ostriches (Struthio camelus) at two different dose rates. J Vet Sci 2006 Dec;7(4):327-32.
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