Ocular penetration and pharmacokinetics of topical clarithromycin eye drops to rabbits.

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.