Prolonged Exposure to Loteprednol Etabonate in Human Tear Fluid and Rabbit Ocular Tissues Following Topical Ocular Administration of Lotemax Gel, 0.5%

Abstract

The gel formulation of LE provided prolonged exposure to LE on the ocular surface, with measurable levels in tears through 24 h in both humans and rabbits, for delivery of LE to anterior segment tissues, as evidenced by sustained levels of LE in rabbit conjunctiva, cornea, and iris/ciliary body.

Loteprednol etabonate for inflammatory conditions of the anterior segment of the eye: twenty years of clinical experience with a retrometabolically designed corticosteroid

“…In rabbit models, the highest concentrations of LE were detected in the cornea and conjunctiva, followed by the iris/ ciliary body, and much lower levels in the aqueous humor (100-fold lower than corneal concentrations) [13,16]. Studies in human subjects noted measurable levels of LE in tear fluid through 24 h after instillation [17] and plasma levels of LE and…”

“…The gel has a unique rheological nature that allows it to be instilled as a viscous drop, after which it transitions to a fluid state on the surface of the eye, and also contains polycarbophil, a mucoadhesive polymer designed to prolong ocular surface retention time. LE was detected in tear fluid for 24 h following gel instillation in both rabbits and human volunteers [17]. LE gel has a homogenous composition, and, compared with LE suspension, a lower concentration of the preservative benzalkonium chloride (0.003% vs. 0.01%), a more physiologic pH, (6.5 vs. 5.5) and does not need to be resuspended by shaking prior to administration [57].…”

Loteprednol Etabonate for the Treatment of Dry Eye Disease

“…29 While LE has been shown to penetrate efficiently into the aqueous humor following topical ocular instillation of either the suspension or gel formulations, the highest concentrations of LE are consistently achieved on the ocular surface (cornea and conjunctiva). [43][44][45][46] As attested herein, multiple studies have evaluated LE suspension and gel formulations for the treatment of DED stemming from various causes and have also investigated its efficacy as induction therapy in reducing stinging associated with topical CsA in DED. In the 14 reviewed LE suspension 0.5% studies, dosing regimens were BID (5 studies), 49,53,54,56,60 QID (6 studies), 47,48,52,[57][58][59] QID (induction therapy for CsA) followed by BID (in conjunction with CsA; 1 study), 22 or tapered from BID to every other day (2 studies) 50,51 and ranged from 15 days 52 to 2 years.…”

“…43 In addition, measurable concentrations of LE were detected in tear fluid through 24 h after topical administration of LE gel 0.5% in both rabbits and humans. 46 The TFOS DEWS II staged management and treatment recommendations include a 4-step process for the management of DED (Table 2). These guidelines suggest that repeated short-term pulse therapy of corticosteroids can be an alternative approach (step 2) for patients with moderate-to-severe DED not controlled with other therapies.…”

“…The LE gel formulations also contain lower concentrations of the preservative benzalkonium chloride (BAK) compared with LE ophthalmic suspension 0.5% and 1% and have a pH close to that of tears, 33 , 36 , 43 which may be beneficial when treating ocular surface disorders. Pharmacokinetic studies in rabbits demonstrated that LE was present at high concentrations in the cornea and conjunctiva through 24 h following topical administration of LE 0.5% suspension, 44 , 45 LE gel 0.5%, 46 and LE gel 0.38%. 43 In addition, measurable concentrations of LE were detected in tear fluid through 24 h after topical administration of LE gel 0.5% in both rabbits and humans.…”