Diflucortolone

Absorption

The absorption of diflucortolone is made mainly percutaneously but it may be absorbed systemically. The absorption and bioavailability of diflucortolone will be related to the type of formulation found in the medication. The percutaneous absorption depends on the vehicle, dose, treatment area, duration of treatment, the condition of treatment, the status of penetration barrier and localization of treated area in the body. Thus, rectal administration of diflucortolone produces a slow and low absorption with an AUC, Cmax and Tmax of 10.8 ng h/ml, 0.75 ng/ml and 4.7 h, respectively.

Toxicity

Diflucortolone can cause skin irritation, vesicles or red patches on the skin.

Originator

Nerisone,Schering,UK,1976

The Uses of Diflucortolone

Glucocorticoid. .

The Uses of Diflucortolone

Difluocortolone is used as a topical therapy in the treatment of pediatric tinea corporis; a common mycotic infection in children.

Indications

Difluocortolone is used as a topical treatment of the symptoms of inflammatory skin disorders like eczema, seborrheic eczema, lichen planus and psoriasis. All these disorders present as a common characteristic the occurrence of symptoms as itching, swelling, redness and scaling.

Background

Difluocortolone is a potent topical corticosteroid. It is commonly used in dermatology for the reduction of inflammation and itching. It was submitted to the FDA in July 1984 by the pharmaceutical company Schering AG.

Definition

ChEBI: Diflucortolone is a 21-hydroxy steroid.

Manufacturing Process

16α-Methyl-6α,9α-difluoro-δ4-pregnene-11α,21-diol-3,20-dione-21-acetate (MP = 229°/232°-234°C (with decomposition) is dehydrogenated in 1.2- position by means of Bacillus lentus, Mutant MB 284, whereby the 21-acetate group is simultaneously saponified. (It is possible under the same conditions to start with the free 21-hydroxyl compound.)
For this purpose a fermenter made of stainless steel having a 50 liter capacity is charged with 30 liters of a nutrient solution of 0.1% yeast extract, 0.5% cornsteep and 0.2% glucose, heated for one-half hour at 120°C for sterilization purposes, and after cooling, inoculated with a bacterial suspension of Bacillus lentus MB 284.
After 24 hours of growth at 28°C under stirring (220 revolutions per minute) and aeration (1.65 m3/hr), 1.8 liters of the obtained culture is removed under sterile conditions and transferred with 28 liters of the same sterilized nutrient medium into a fermenter of the same size.
Simultaneously, 6 g of 16α-methyl-6α,9α-difluoro-δ4-pregnene-11β,21-diol3,20-dione-21-acetate in 200 cc of dimethylformamide are added and the fermentation is continued for 50 hours under the same conditions.
The course of the fermentation is tested by removal of samples which are extracted with methyl isobutyl ketone. The extracts are analyzed by thin layer chromatography using a system of benzene/ethyl acetate (4:1).
After further working up there is obtained an oily crystalline residue which is subjected to chromatography on silica gel. The 16α-methyl-6α,9α-difluoroδ1,4-pregnadien-11β,21-diol-3,20-dione is eluated with ethyl acetatechloroform (1:2), it is recrystallized from ethyl acetate/ether and then formed to melt at 240°/242°-244°C. The yield is 60% of the theoretical. The product is reacted with valeric acid chloride to give the valerate ester.

Therapeutic Function

Antiinflammatory

Pharmacokinetics

Diflucortolone is a steroid with the properties of being an anti-inflammatory, antipruritic and vasoconstrictive. Its activity causes the vasoconstriction of the blood vessels and thus a decrease in the release of inflammatory substances. These actions produce the effect of skin soothed and elimination of the symptoms.

Metabolism

The metabolism of diflucortolone is done in the liver where it is very rapidly degraded. After 5 minutes of administration of diflucortolone in a dose of 1mg, there is a concentration of intact diflucortolone in plasma of 6-8 ng/ml. The analysis of the metabolites showed the presence of 11-keto-diflucortolone as the major metabolite in the plasma.