Loteprednol
Loteprednol (as the ester loteprednol etabonate) is a corticosteroid used to treat inflammations of the eye. It is marketed by Bausch and Lomb as Lotemax and Loterex. It was patented in 1980 and approved for medical use in 1998. Medical uses. Applications for this drug include the reduction of inflammation after eye surgery, seasonal allergic conjunctivitis, uveitis, as well as chronic forms of keratitis (e.g. adenoviral and Thygeson's keratitis), vernal keratoconjunctivitis, pingueculitis, and episcleritis. Contraindications. As corticosteroids are immunosuppressive, loteprednol is contraindicated in patients with viral, fungal or mycobacterial infections of the eye. Adverse effects. The most common  adverse effects in patients being treated with the gel formulation are anterior chamber inflammation (in 5% of people), eye pain (2%), and foreign body sensation (2%). Interactions. Because long term use (more than 10 days) can cause increased intraocular pressure, loteprednol may interfere with the treatment of glaucoma. Following ocular administration, the drug is very slowly absorbed into the blood, therefore the blood level is limited to an extremely small concentration, and interactions with drugs taken by mouth or through any route other than topical ophthalmic are very unlikely. Pharmacology. Pharmacokinetics. Neither loteprednol etabonate nor its inactive metabolites Δ-cortienic  acid and Δ-cortienic acid etabonate are detectable in the bloodstream, even after oral administration. A study with patients receiving loteprednol eye drops over 42 days showed no adrenal suppression, which would be a sign of the drug reaching the bloodstream to a clinically relevant extent. Steroid receptor affinity was 4.3 times that of dexamethasone in animal studies. Retrometabolic drug design. Loteprednol etabonate was developed using retrometabolic drug design. It is a so-called soft drug, meaning its structure was designed so that it is predictably metabolised to inactive substances. These metabolites, Δ-cortienic acid and its etabonate, are derivatives  of cortienic acid, itself an inactive metabolite of hydrocortisone. Chemistry. Loteprednol etabonate is an ester of loteprednol with etabonate (ethyl carbonate). The pure chemical compound has a melting point between and . Its solubility in water is 1:2,000,000, therefore it is formulated for ophthalmic use as either an ointment, a gel, or a suspension. Loteprednol is a corticosteroid. The ketone side chain of classical corticosteroids such as hydrocortisone is replaced by a cleavable ester, which accounts for the rapid inactivation. (This is not the same as the etabonate ester.)