Method for reducing side effects from administration of phosphodiesterase-4 inhibitors
A method for altering the PK profile of a pharmaceutical formulation containing a PDE-4 inhibitor, such as roflumilast, to reduce the spike in Cmax. The spike in Cmax is reduced by topically administering the PDE-4 inhibitor in combination with one or more phosphate ester surfactants. Reducing the spike in Cmax will reduce gastrointestinal side effects and result in better patient compliance.
1 . A method of treating a patient suffering from an inflammatory dermatosis comprising:
topically administering to said patient a cream once per day, wherein the cream comprises 0.05% w/w roflumilast, diethylene glycol monoethyl ether, and an emulsifier blend comprising cetostearyl alcohol, dicetyl phosphate and ceteth-10 phosphate,
wherein roflumilast blood plasma concentration peak to trough ratio is less than 2 after 4 weeks of once-daily administration.
2 . The method according to claim 1 , wherein the cream comprises about 10% w/w of said emulsifier blend.
3 . The method according to claim 2 , wherein the cream comprises about 25% w/w diethylene glycol monoethyl ether.
4 . The method according to claim 3 , wherein the cream further comprises about 2% w/w hexylene glycol.
5 . The method according to claim 4 , wherein the inflammatory dermatosis is atopic dermatitis.
6 . The method according to claim 4 , wherein the inflammatory dermatosis is psoriasis.
7 . The method according to claim 3 , wherein the inflammatory dermatosis is atopic dermatitis.
8 . The method according to claim 3 , wherein the inflammatory dermatosis is psoriasis.
9 . The method according to claim 1 , wherein the inflammatory dermatosis is atopic dermatitis.
10 . The method according to claim 1 , wherein the inflammatory dermatosis is psoriasis.
11 . A method of treating a patient suffering from an inflammatory dermatosis comprising:
topically administering to said patient a cream comprising a 0.05% w/w roflumilast, diethylene glycol monoethyl ether, and an emulsifier blend comprising cetostearyl alcohol, dicetyl phosphate and ceteth-10 phosphate,
wherein the Cmax of roflumilast from the topical composition is reduced relative to an oral roflumilast formulation marketed under the trademark DALIRESP®.
12 . The method according to claim 11 , wherein the cream is administered once or twice daily.
13 . The method according to claim 12 , wherein the cream is administered once daily.
14 . The method according to claim 13 , wherein the cream comprises about 10% w/w of said emulsifier blend.
15 . The method according to claim 14 , wherein the cream comprises about 25% w/w diethylene glycol monoethyl ether.
16 . The method according to claim 15 , wherein the cream further comprises about 2% w/w hexylene glycol.
17 . The method according to claim 16 , wherein the inflammatory dermatosis is atopic dermatitis.
18 . The method according to claim 16 , wherein the inflammatory dermatosis is psoriasis.
19 . The method according to claim 15 , wherein the inflammatory dermatosis is atopic dermatitis.
20 . The method according to claim 15 , wherein the inflammatory dermatosis is psoriasis.
21 . The method according to claim 11 , wherein the inflammatory dermatosis is atopic dermatitis.
22 . The method according to claim 11 , wherein the inflammatory dermatosis is psoriasis.