Abstract / Summary
Abstract Drug-loaded contact lenses have emerged as a promising alternative for ocular drug delivery, but direct evidence that lens delivery increases ocular exposure of lifitegrast remains limited. This study compared ocular and systemic exposure to lifitegrast delivered using an eye-drop solution and two prototype contact lens loading configurations in rabbits. An eye drop (0.4 mg/eye), a chamber-loaded lens (0.4 mg/eye), and a surface-loaded lens (1.25 mg/eye) were administered to New Zealand white rabbits, and lifitegrast in plasma, cornea, conjunctiva, sclera, and aqueous humor was quantified by LC-MS/MS. In vitro and in vivo drug release from the lenses was also determined. A release-linked population pharmacokinetic model incorporating distinct input pathways for the two lens configurations was used to characterize corneal exposure. The components of the drug solution were classified as non-irritant in an ocular irritation assay. Both lens formulations increased systemic and ocular exposure relative to the eye drop, with dose-normalized corneal AUC last (0–12 h for the lenses; 0–8 h for the eye drop) increasing 3-fold with the chamber-loaded lens and 111-fold with the surface-loaded lens. The model estimated apparent precorneal elimination rate constants of 4.64 and 2.19 h − 1 for the eye drop and lens regimens, respectively. In conclusion, this study demonstrates the potential of contact lens delivery to increase ocular tissue exposure to lifitegrast, offering a strategy to overcome the pharmacokinetic limitations of conventional eye drops.