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An ophthalmic corticosteroid. Used as an anti-inflammatory

Biological Activity Chemical Information Tech Support & FAQs Biological Activity Loteprednol etabonate is an anti-inflammatory corticosteroid used in ophthalmology. It is used for the treatment of steroid responsive inflammatory conditions of the eye su

Pharmos (US)

ChEBI: Loteprednol etabonate is an etabonate ester, an 11beta-hydroxy steroid, a steroid ester, an organochlorine compound, a steroid acid ester and a 3-oxo-Delta(1),Delta(4)-steroid. It has a role as an anti-inflammatory drug. It is functionally related to a loteprednol.

To a solution of hydrocortisone (15 g, 0.04 mol) in 120 ml of THF and 30 ml of methanol at room temperature is added a warm solution of sodium metaperiodate (25.7 g, 0.12 mol) in 100 ml of water. The reaction mixture is stirred at room temperature for 2 hours, then is concentrated under reduced pressure to remove the tetrahydrofuran and methanol. The solid is triturated with 50 ml of water, separated by filtration, washed with water and dried in vacuo at 50°C for 3 hours. The product, 11β,17α-dihydroxyandrost-4-en-3- one-17β-carboxylic acid (i.e., cortienic acid), is obtained in approximately 96% yield (13.76 g); melting point 231-234°C.
To a cold solution of 11β,17α-dihydroxyandrost-4-en-3-one-17β-carboxylic acid (5% weight/volume; 1 mol) and triethylamine (4 mol) in dichloromethane is added a 50% (weight/volume) solution of ethyl chloroformate (3.9 mol) in dichloromethane. The reaction mixture is allowed to warm to room temperature over a 2 hour period. The triethylamine hydrochloride precipitate which forms is removed by filtration and the filtration is washed successively with 3% sodium bicarbonate, 1% hydrochloric acid and water. The organic layer is separated, dried with magnesium sulfate, and filtered. The filtrate is concentrated in vacuo to a foam.
The foam is used in the next step below or chromatographed and crystallized for analysis. The product 17α-ethoxycarbonyloxy-11β-hydroxyandrost-4-en-3- one-17β-carboxylic acid, melting at 192-195°C C after chromatography and crystallization.
17α-Ethoxycarbonyloxy-11β-hydroxyandrost-4-en-3-one-17β-carboxylic acid is combined with an equivalent amount of 1 N sodium hydroxide in methanol and that solution is diluted to 100 times the original volume with ethyl ether. The suspension which results is refrigerated for 1 hour. Then, the crystals which form are removed by filtration, dried in an evacuated desiccator, and dissolved in hexamethylphosphoramide (10% weight/volume). A portion of the resultant solution containing 1 mole of the acid salt, i.e. of sodium 17αethoxycarbonyloxy-11β-hydroxyandrost-4-en-3-one-17β-carboxylate, is combined with 4 moles of chloromethyl iodide. The reaction mixture is maintained at room temperature for 3 hours, then is diluted to 10 times the original volume with ethyl acetate. The diluted reaction mixture is washed successively with 5% sodium thiosulfate, 3% sodium bicarbonate, and water. The organic layer is separated, dried with magnesium sulfate and filtered. The filtrate is concentrated in vacuo to a foam. The foam is purified by crystallization from ethyl ether or tetrahydrofuran/hexane. There is thus obtained chloromethyl-17α-ethoxycarbonyloxy-11β-hydroxyandrost-4-en-3- one-17β-carboxylate, melting at 197-200°C after crystallization.

Alrex (Bausch & Lomb); Lotemax (Bausch & Lomb); Lotemax (Pharmos);Lotemax (0.5%）.

Glucocorticoid

Loteprednol etabonate,chloromethyl 17α-[(ethoxycarbonyl)oxy]-11β-hydroxy-3-oxoandrosta-1,4-diene-17-carboxylate (Alrex,Lotemax), has a modified carboxylate at the C17 positionrather than the typical ketone functionality. This modificationmaintains affinity for the GR but allows facile metabolismto inactive metabolites. This limits the systemic actionof the drug. Loteprednol etabonate is used as anophthalmic suspension that has greatly reduced systemicaction because of rapid metabolism to the inactive carboxylate.

Loteprednol Etabonate is an anti-inflammatory corticosteroid (ophthalmology).