Topical Application of a Novel Harderian-Derived Nonpolar Lipid Prolongs Tear Film Breakup Time in Normal Beagle Dogs.

PURPOSE: This preliminary study sought to determine the pharmacodynamic effect and tolerability of a novel rabbit-derived nonpolar lipid (rNPL593) on tear film breakup time (TFBUT) in healthy beagle dogs as a potential therapy for patients with evaporative dry eye disease.

METHODS

In phase 1, two healthy beagle dogs received a single dose of rNPL593 at concentrations ranging from 0.1 to 10 mg/mL, and TFBUT was measured at different intervals post-dose in both eyes. In phase 2, five dogs received vehicle, 1 or 3 mg/mL rNPL593 once in both eyes, and TFBUT was measured at 6- and 24-h post-dose. In phase 3, three dogs received multiple doses of 3 mg/mL rNPL593 over 4 days, and TFBUT was performed 6 and 80 h after the final dose. Semiquantitative preclinical ocular toxicology scoring was performed in all phases to determine tolerability.

RESULTS

In phase 1, topical treatment with 3 mg/mL rNPL593 resulted in a dose-dependent increase in TFBUT, assessed as the preferred concentration. In phase 2, the concentration of 3 mg/mL was superior to 1 mg/mL by creating a more pronounced and sustained increase in TFBUT over 24 h. In phase 3, there was an increase in TFBUT measured at 6-h post-dose that returned to baseline levels at 80-h post-dose. The topical rNPL593 was well tolerated in all phases with all doses.

CONCLUSIONS

Treatment with rNPL593 was well tolerated at all doses tested and resulted in an increased TFBUT that was most pronounced with the 3 mg/mL concentration at 6- and 24-h post-dose.