Pharmacokinetics and distribution of minocycline in mature horses after oral administration of multiple doses and comparison with minimum inhibitory concentrations.
Abstract: Minocycline holds great potential for use in horses not only for its antimicrobial effects but also for its anti-inflammatory and neuroprotective properties. However, there are no pharmacokinetic or safety data available regarding the use of oral minocycline in horses. Objective: To determine pharmacokinetics, safety and penetration into plasma, synovial fluid, aqueous humour (AH) and cerebral spinal fluid (CSF) of minocycline after oral administration of multiple doses in horses and to determine the minimum inhibitory concentrations (MIC) of minocycline for equine pathogenic bacteria. Methods: Six horses received minocycline (4 mg/kg bwt q. 12 h for 5 doses). Thirty-three blood and 9 synovial fluid samples were collected over 96 h. Aqueous humour and CSF samples were collected 1 h after the final dose. Minocycline concentrations were measured using high pressure liquid chromatography. The MIC values of minocycline for equine bacterial isolates were determined. Results: At steady state, the mean ± s.d. peak concentration of minocycline in the plasma was 0.67 ± 0.26 µg/ml and the mean half-life was 11.48 ± 3.23 h. The highest trough synovial fluid minocycline concentration was 0.33 ± 0.12 µg/ml. The AH concentration of minocycline was 0.09 ± 0.03 µg/ml in normal eyes and 0.11 ± 0.04 µg/ml in blood aqueous barrier-disrupted eyes. The mean CSF concentration of minocycline was 0.38 ± 0.09 µg/ml. The MIC values were determined for 301 isolates. Minocycline concentrations were above the MIC(50) and MIC(90) for many gram-positive equine pathogens. Conclusions: This study supports the use of orally administered minocycline at a dose of 4 mg/kg bwt every 12 h for the treatment of nonocular infections caused by susceptible (MIC ≤ 0.25 µg/ml) organisms in horses. Further studies are required to determine the dose that would be effective for the treatment of ocular infections.
© 2011 EVJ Ltd.
Publication Date: 2011-09-25 PubMed ID: 21950341DOI: 10.1111/j.2042-3306.2011.00459.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research conducts an investigation into the pharmacokinetics, safety, and penetration of minocycline in horses following oral administration over multiple doses. The study supports the use of oral minocycline for treatment of non-ocular infections in horses, yet highlights the necessity for further research to establish effective dosing for the treatment of ocular infections.
Study Objective and Methods
- The objective of this study was to uncover the pharmacokinetics, safety, and penetration of minocycline into different body fluids like plasma, synovial fluid, aqueous humour, and cerebral spinal fluid in horses upon oral administration.
- The study involved administering six horses with oral minocycline in doses of 4 mg/kg bodyweight every 12 hours over five doses.
- Researchers collected thirty-three blood and nine synovial fluid samples over a period of 96 hours, and aqueous humour and CSF samples were collected an hour after the final dose.
Measurement and Analysis
- Using high-pressure liquid chromatography, minocycline concentrations in various samples were identified and measured.
- The study also determined the minimum inhibitory concentrations (MIC) for minocycline against equine pathogenic bacteria with 301 bacterial isolates used to determine the MIC values.
Result Report
- The peak concentration of minocycline in the plasma was 0.67 ± 0.26 µg/ml, while the mean half-life was around 11.48 hours.
- The highest trough synovial fluid minocycline concentration was 0.33 ± 0.12 µg/ml, and it was present at levels of 0.09 ± 0.03 µg/ml in normal eyes’ aqueous humour and 0.11 ± 0.04 µg/ml in blood aqueous barrier-disrupted eyes.
- The mean CSF concentration of minocycline was 0.38 ± 0.09 µg/ml.
- Minocycline concentrations were observed to be greater than MIC(50) and MIC(90) for numerous gram-positive equine pathogens.
Conclusions and Implications
- The study supports the use of orally administered minocycline at a dosage of 4 mg/kg bodyweight every 12 hours for treating nonocular infections in horses due to susceptible (MIC ≤ 0.25 µg/ml) organisms.
- Nonetheless, more research is needed to determine the efficient dose for treatment of minocycline in ocular infections.
Cite This Article
APA
Schnabel LV, Papich MG, Divers TJ, Altier C, Aprea MS, McCarrel TM, Fortier LA.
(2011).
Pharmacokinetics and distribution of minocycline in mature horses after oral administration of multiple doses and comparison with minimum inhibitory concentrations.
Equine Vet J, 44(4), 453-458.
https://doi.org/10.1111/j.2042-3306.2011.00459.x Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
MeSH Terms
- Administration, Oral
- Animals
- Anti-Bacterial Agents / administration & dosage
- Anti-Bacterial Agents / pharmacokinetics
- Aqueous Humor / chemistry
- Area Under Curve
- Bacteria / drug effects
- Drug Administration Schedule
- Female
- Half-Life
- Horses / blood
- Horses / cerebrospinal fluid
- Horses / metabolism
- Male
- Microbial Sensitivity Tests
- Minocycline / administration & dosage
- Minocycline / chemistry
- Minocycline / pharmacokinetics
- Pilot Projects
- Synovial Fluid / chemistry
- Tissue Distribution
Citations
This article has been cited 4 times.- 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.
- Zhou J, Ledesma KR, Chang KT, Abodakpi H, Gao S, Tam VH. Pharmacokinetics and Pharmacodynamics of Minocycline against Acinetobacter baumannii in a Neutropenic Murine Pneumonia Model.. Antimicrob Agents Chemother 2017 May;61(5).
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