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

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 (Cmax) 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 Cmax, 0.97 µg/g; multiple-dose Cmax, 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.