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

Abstract

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.