Evaluation of Pharmacokinetic Profile of Novel Ophthalmic Formulation of Loteprednol Etabonate
Narrative Responses:
Purpose
The purpose of these studies was to evaluate the ocular pharmacokinetic (PK) profile of a novel formulation of loteprednol etabonate that uses a proprietary mucus penetrating particle (MPP) technology. The PK profile of loteprednol etabonate was evaluated after a QD, BID and QID dosing regimen.
Methods
A rabbit model was used for these PK studies. A single drop (QD) of either loteprednol etabonate ophthalmic suspension MPP (LE-MPP) 0.4% or LOTEMAX®-brand loteprednol etabonate ophthalmic gel 0.5% (LE gel) was administered to one group of rabbits. A second group of rabbits received LE-MPP 0.4% either BID or QID. Samples of the aqueous humor and cornea were collected over a 12 hour period after a single administration of the test article for QD animal groups, and 8 hours after the last administration for BID/QID animal groups. Loteprednol etabonate concentrations were assayed by liquid chromatography–tandem mass spectrometry (LC/MS/MS).
Results
Seventy-eight rabbits (156 eyes) were used for the PK analysis. After a single drop, peak concentrations of loteprednol etabonate in the cornea and aqueous humor were 2580 ng/g and 30.3 ng/mL for LE-MPP 0.4%, and 1470 ng/g and 12.7 ng/mL for the LE gel. Following instillation of multiple drops (BID or QID dosing regimen), peak levels of loteprednol etabonate in the cornea and aqueous humor were 1392 ng/g and 28.3 ng/mL for BID, and 1672 ng/g and 30.3 ng/mL for QID administration of LE-MPP 0.4%.
Conclusion
In these rabbit studies, high levels of loteprednol etabonate were achieved in the cornea and aqueous humor following topical administration of a novel MPP ophthalmic formulation. These preclinical data indicate penetration of ocular mucosal barriers may present an opportunity to enhance effective drug levels in ocular tissue through topical administration.