Ocular Pharmacokinetics and Biodistribution of Perfluorohexyloctane after Topical Administration to Rabbits.

Abstract

Purpose: Perfluorohexyloctane ophthalmical solution (PFHO) forms an anti-evaporative layer at the air-tear interface and is indicated for treatment of the signs and symptoms of dry eye disease (DED). This study evaluated the ocular pharmacokinetics and biodistribution of PFHO in rabbits. Methods: Radiolabeled PFHO was administered to female Dutch Belted rabbits as single (35 µL to each eye) or multiple (twice daily for 5 days) topical ocular doses. Animals were euthanized at designated timepoints. Tears (antemortem), ocular tissues, and blood were collected for pharmacokinetic analysis; heads and carcasses were collected for autoradiographic analysis. Concentrations were measured using liquid scintillation counting. Results: After multiple doses, maximum concentration (C_max) and area under the concentration-time curve were highest in tears (2330 µg/g, 3720 µg•h/g) and Meibomian glands (222 µg/g, 1440 µg•h/g), followed by other anterior tissues (cornea, 27.6 µg/g, 463 µg•h/g; palpebral conjunctiva, 14.0 µg/g, 136 µg•h/g). PFHO was measurable in tears for 8 h and in Meibomian glands for ≥24 h. Distribution to the posterior ocular segment was minimal, and plasma concentrations were low (single-dose C_max, 0.97 µg/g; multiple-dose C_max, 3.2 µg/g). In non-ocular tissues, PFHO was confined primarily to nasal tissues and gastrointestinal tract contents; exposure to other systemic tissues was negligible. Conclusions: Exposure of PFHO was highest in tears, consistent with its anti-evaporative mode of action, followed by the Meibomian glands. PFHO exposure was very low in posterior ocular tissues and negligible in systemic circulation, consistent with the clinical safety profile.