Loteprednol etabonate is a
corticosteroid which is the product of 'soft
drug' design (synthesis of a compound that undergoes predictable metabolism to inactive metabolites after its
therapeutic effects have been expressed at or near the site of application). It has been developed as a topical treatment for ocular
inflammation.
Loteprednol etabonate is designed to be rapidly converted to inactive and nontoxic metabolites, thus minimising systemic adverse effects. The concentration of the
drug in plasma from 10 healthy volunteers who received ocular
loteprednol etabonate at therapeutic or supratherapeutic dosages was below the limit of detection. In 2 double-masked, placebo-controlled studies,
loteprednol etabonate 0.5% 4 times daily (1
drop/eye) for 2 weeks was more effective than placebo in relieving moderate to severe postoperative ocular
inflammation after
cataract surgery. The same regimen was also effective when administered for up to 6 weeks in 3 double-masked placebo-controlled studies in patients with moderate or severe
contact lens-associated
giant papillary conjunctivitis. Data from 2 double-masked placebo-controlled studies indicate that
loteprednol etabonate 0.2% (1
drop/eye 4 times daily for 2 weeks) is effective in patients with moderate to severe seasonal
allergic conjunctivitis. Furthermore, a single placebo-controlled trial has shown that
loteprednol etabonate 0.5% has prophylactic efficacy in patients with a history of seasonal
allergic conjunctivitis. Ocular
loteprednol etabonate was well tolerated, both locally and systemically, in clinical trials reported to date. Elevated intraocular pressure (IOP) is possible after
ocular administration of the
drug but is infrequent overall: only 1.7% of 901 patients or volunteers who received
loteprednol 0.2 or 0.5% for >or=28 days had a clinically significant increase (>or=10mm Hg) in IOP. Unlike
prednisolone acetate,
loteprednol etabonate did not significantly increase IOP from baseline in a small randomised crossover study in known
steroid responders. There were no serious or unexpected treatment-related ocular adverse events in patients receiving
loteprednol etabonate in clinical trials. The potential for
cataract formation or
glaucoma after long term treatment is unknown. Thus,
loteprednol etabonate can reduce ocular
inflammation caused by
cataract surgery, seasonal
allergic conjunctivitis or
contact lens wear. The benign tolerability profile of
loteprednol etabonate, in particular its low propensity to cause elevated IOP (when used in the short term) is an attractive characteristic. However, the place of
loteprednol etabonate in clinical practice cannot be properly assessed until direct efficacy comparisons with other active treatments are available.