Caroline S Monk1, Sun Young Jeong2, Daniel James Gibson2, Caryn E Plummer1,3. 1. Department of Small Animal Clinical Sciences, University of Florida College of Veterinary Medicine, Gainesville, FL, USA. 2. Department of Obstetrics, Shands School of Medicine, University of Florida, Gainesville, FL, USA. 3. Department of Large Animal Clinical Sciences, University of Florida College of Veterinary Medicine, Gainesville, FL, USA.
Abstract
PURPOSE: 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.
PURPOSE: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 humanMMP-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.
Authors: Lionel Sebbag; Lucas Showman; Emily M McDowell; Ann Perera; Jonathan P Mochel Journal: J Ocul Pharmacol Ther Date: 2018-04-30 Impact factor: 2.671
Authors: Mennatallah A Mohamed; Maha Nasr; Walid F Elkhatib; Wafaa N Eltayeb; Aliaa A Elshamy; Gharieb S El-Sayyad Journal: RSC Adv Date: 2021-12-13 Impact factor: 4.036