Lotemax Mechanism of Action

Topical anti-inflammatory corticosteroid for ophthalmic use.
Pharmacology: Corticosteroids inhibit the inflammatory response to a variety of inciting agents and probably delay or slow healing. They inhibit edema, fibrin deposition, capillary dilation, leukocyte migration, capillary and fibroblast proliferation, deposition of collagen and scar formation associated with inflammation.
There is no generally accepted explanation for the mechanism of action of ocular corticosteroids. However, corticosteroids are thought to act by the induction of phospholipase A₂ inhibitory proteins, collectively called as lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation eg, prostaglandins and leukotrienes, by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A₂. Corticosteroids are capable of producing a rise in intraocular pressure.
Loteprednol etabonate is structurally similar to other corticosteroids. However, the number 20 position ketone group is absent. It is highly lipid soluble which enhances its penetration into cells. Loteprednol etabonate is synthesized through structural modifications of prednisolone-related compounds so that it will undergo a predictable transformation to an inactive metabolite. Based upon in vivo and in vitro preclinical metabolism studies, loteprednol etabonate undergoes extensive metabolism to inactive carboxylic acid metabolites.
Results from a bioavailability study in normal volunteers established that plasma levels of loteprednol etabonate and δ¹-cortienic acid etabonate (PJ 91), its primary inactive metabolite, were below the limit of quantitation (1 ng/mL) at all sampling times. The results were obtained following the ocular administration of 1 drop in each eye of 0.5% loteprednol etabonate 8 times daily for 2 days or 4 times daily for 42 days. This study suggests that limited (<1 ng/mL) systemic absorption occurs with Lotemax.
Clinical Studies: Postoperative Inflammation: Placebo-controlled clinical studies demonstrated that Lotemax is effective for the treatment of anterior chamber inflammation as measured by cell and flare.
Giant Papillary Conjunctivitis: Placebo-controlled clinical studies demonstrated that Lotemax was effective in reducing the signs and symptoms of giant papillary conjunctivitis after 1 week of treatment and continuing for up to 6 weeks while on treatment.
Seasonal Allergic Conjunctivitis: A placebo-controlled clinical study demonstrated that Lotemax was effective in reducing the signs and symptoms of allergic conjunctivitis during peak periods of pollen exposure.
Uveitis: Controlled clinical studies of patients with uveitis demonstrated that Lotemax was less effective than prednisolone acetate 1%. Overall, 72% of patients treated with Lotemax experienced resolution of anterior chamber cell by day 28, compared to 87% of patients treated with prednisolone acetate 1%. The incidence of patients with clinically significant increases in intraocular pressure (IOP) (≥10 mm HG) was 1% with Lotemax and 6% with prednisolone acetate 1%.