The presence of minocycline in the tear film of normal horses following oral administration and its anticollagenase activity.
Abstract: Tetracyclines have activity against matrix metalloproteinases (MMP). Oral medications with effects on the ocular surface are of interest in patients where repeated topical dosing is limited. The aim of this study was to characterize the concentration of minocycline in the tears of normal horses after oral administration and to determine if this level directly inhibits MMP activity. Methods: Five healthy adult ponies were administered oral minocycline (Wedgewood Pharmacy; Swedesboro, NJ) at 4 mg/kg every 12 h for 5 days. Tears were collected at T = 2, 26, 50, 56, 74, 80, and 98 h. Tear minocycline concentrations were analyzed using high performance liquid chromatography. The inhibition of recombinant human MMP-2 and MMP-9 by minocycline was investigated using fluorescence resonance energy transfer. Results: Minocycline was present in the tears of each pony at every measurement but with interpony variability. A mean concentration of 11.8 μg/mL was present 2 h after administration of the first dose. Minocycline did not directly inhibit MMP-2 or MMP-9 function at a concentration achieved in the pony tear film. Conclusions: Minocycline was present in the tears of all ponies at each sampling point following oral administration. One pony of the five had consistently lower levels of minocycline secretion (P ≤ 0.05). The concentration secreted in the tears did not directly inhibit MMP-2 or MMP-9 when tested in vitro. The inconsistencies in the tear concentration and the inhibition activity suggest topical application may be necessary to attain direct inhibition of MMP with minocycline.
© 2017 American College of Veterinary Ophthalmologists.
Publication Date: 2017-06-09 PubMed ID: 28598549DOI: 10.1111/vop.12479Google Scholar: Lookup
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- Clinical Trial
- Journal Article
Summary
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The study investigates the concentration of the antibiotic minocycline in horse tears after oral administration, and determines its effectiveness in directly inhibiting matrix metalloproteinases (MMPs). It was found that minocycline appears in the tears, even though it varied between horses, but was ineffective at inhibiting MMPs at the given concentration.
Methodology
- Five healthy adult ponies were orally administered minocycline at 4 mg/kg every 12 hours for five days.
- At various time intervals, the researchers collected tear samples from the ponies to study the concentration of minocycline.
- The concentration of minocycline in the tears was analyzed using high performance liquid chromatography.
- In order to determine the ability of minocycline to inhibit the action of MMPs, a fluorescence resonance energy transfer investigation was conducted using recombinant human MMP-2 and MMP-9.
Results
- Minocycline was found in the tear samples of all five ponies. However, there was variability in the concentration between different ponies.
- Two hours after the first dosage of minocycline was given, an average concentration of 11.8 μg/mL was observed in the tears.
- Despite the presence of minocycline in the tears, it did not directly inhibit the function of MMP-2 or MMP-9 enzymes at the concentration measured in the tears.
Conclusions
- Minocycline was present in the tears of all ponies at each time point following oral administration. However, one pony consistently had lower levels of minocycline.
- The concentration of minocycline secreted in the tears did not directly inhibit MMP-2 or MMP-9 when tested in vitro.
- The varying concentrations of minocycline and the lack of MMP inhibition suggest that topical application may be needed to attain direct inhibition of MMP with minocycline.
Cite This Article
APA
Monk CS, Jeong SY, Gibson DJ, Plummer CE.
(2017).
The presence of minocycline in the tear film of normal horses following oral administration and its anticollagenase activity.
Vet Ophthalmol, 21(1), 58-65.
https://doi.org/10.1111/vop.12479 Publication
Researcher Affiliations
- Department of Small Animal Clinical Sciences, University of Florida College of Veterinary Medicine, Gainesville, FL, USA.
- Department of Obstetrics, Shands School of Medicine, University of Florida, Gainesville, FL, USA.
- Department of Obstetrics, Shands School of Medicine, University of Florida, Gainesville, FL, USA.
- Department of Small Animal Clinical Sciences, University of Florida College of Veterinary Medicine, Gainesville, FL, USA.
- Department of Large Animal Clinical Sciences, University of Florida College of Veterinary Medicine, Gainesville, FL, USA.
MeSH Terms
- Administration, Oral
- Animals
- Anti-Bacterial Agents / administration & dosage
- Anti-Bacterial Agents / blood
- Anti-Bacterial Agents / pharmacokinetics
- Anti-Bacterial Agents / therapeutic use
- Corneal Ulcer / drug therapy
- Corneal Ulcer / veterinary
- Female
- Horse Diseases / drug therapy
- Horses / metabolism
- Matrix Metalloproteinases / blood
- Minocycline / administration & dosage
- Minocycline / blood
- Minocycline / pharmacokinetics
- Minocycline / therapeutic use
- Tears / metabolism
Citations
This article has been cited 3 times.- Bowden AC, Allbaugh RA, Smith JS, Mochel JP, Sebbag L. Kinetics and minimal inhibitory concentrations of ceftiofur in tear film following extended-release parenteral administration (Excede(®)) in dogs. Front Vet Sci 2022;9:975113.
- Mohamed MA, Nasr M, Elkhatib WF, Eltayeb WN, Elshamy AA, El-Sayyad GS. Nanobiotic formulations as promising advances for combating MRSA resistance: susceptibilities and post-antibiotic effects of clindamycin, doxycycline, and linezolid. RSC Adv 2021 Dec 13;11(63):39696-39706.
- Sebbag L, Showman L, McDowell EM, Perera A, Mochel JP. Impact of Flow Rate, Collection Devices, and Extraction Methods on Tear Concentrations Following Oral Administration of Doxycycline in Dogs and Cats. J Ocul Pharmacol Ther 2018 Jul Aug;34(6):452-459.
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