PURPOSE: To evaluate the ocular pharmacokinetics of clarithromycin (CLA) eye drops topically applied to the corneas of rabbits. METHODS: One 50-μL drop of CLA (0.25%) was administered to each New Zealand white rabbit in a single dose group, and one 50-μL drop of CLA was administered 6 times at 5-min intervals to each rabbit in a loading dose group. The effect of debridement on corneal penetration was also investigated in a de-epithelium group. The drug concentrations in the cornea and aqueous humor (AH) were assayed using high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) analysis. RESULTS: Maximum CLA levels were achieved in the corneas and AH at 15 and 60 min, respectively, in the intact epithelium eyes in the single dose group (24.54±10.64 μg/g and 0.78±0.22 μg/mL, respectively, mean±the standard error of the mean, n=8). In the loading dose group, 30 min after the last application, the CLA level in the corneas reached 92.26±17.62 μg/g. In the loading dose group, the drug levels in the corneas and AH were significantly increased compared with the drug levels in the corneas with the intact epithelium and de-epithelium eyes in the single dose group at the corresponding time points (P<0.05). The estimated CLA half-lives in the corneas and AH for the intact eyes were 103.28 and 132.61 min, respectively. CONCLUSION: Therapeutic CLA levels can be achieved in rabbit corneas after topically applying the drug with eye drops.
PURPOSE: To evaluate the ocular pharmacokinetics of clarithromycin (CLA) eye drops topically applied to the corneas of rabbits. METHODS: One 50-μL drop of CLA (0.25%) was administered to each New Zealand white rabbit in a single dose group, and one 50-μL drop of CLA was administered 6 times at 5-min intervals to each rabbit in a loading dose group. The effect of debridement on corneal penetration was also investigated in a de-epithelium group. The drug concentrations in the cornea and aqueous humor (AH) were assayed using high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) analysis. RESULTS: Maximum CLA levels were achieved in the corneas and AH at 15 and 60 min, respectively, in the intact epithelium eyes in the single dose group (24.54±10.64 μg/g and 0.78±0.22 μg/mL, respectively, mean±the standard error of the mean, n=8). In the loading dose group, 30 min after the last application, the CLA level in the corneas reached 92.26±17.62 μg/g. In the loading dose group, the drug levels in the corneas and AH were significantly increased compared with the drug levels in the corneas with the intact epithelium and de-epithelium eyes in the single dose group at the corresponding time points (P<0.05). The estimated CLA half-lives in the corneas and AH for the intact eyes were 103.28 and 132.61 min, respectively. CONCLUSION: Therapeutic CLA levels can be achieved in rabbit corneas after topically applying the drug with eye drops.
Authors: J Tuñí-Picado; A Martínez-Palmer; X Fernández-Sala; J Barceló-Vidal; M Castilla-Martí; Y Cartagena-Guardado; S Grau Journal: Rev Esp Quimioter Date: 2018-10-31 Impact factor: 1.553