抄録
A topical NSAID prodrug preparation has not previously been successfully developed because penetration through the skin and activation in the local tissue of prodrug, and a subsequent pharmacological effect could not be obtained. We devised the base for the ointment and cream forms indomethacin farnesil (IND-F, a NSAID prodrug) to include isopropylalcohol, polyalcohol, isotridecyl-myristate, diethyl sebacate, polyethyleneglycol, diisopropanolamine, oxybenzone, carboxy-vinylpolymer and purified water.
The percutaneous absorption of IND-F was confirmed by an increase in the plasma concentration of indomethacin (IND) at 2, 8, and 24 hrs after IND-F application (1.64 mg) to hairless rats. In a rat model of adjuvant arthritis, IND-F ointment and cream produced signicant inhibition of foot edema when compared to the base alone (P<0.01) . In a rat cotton pellet model, there was also significant inhi-bition of the growth of granulation tissue in the IND-F-treated group when compared to the basetreated group (P<0.05) .The clinical efficiency of IND-F ointment was also evaluated in 14 patients with rheumatoid arthritis. Significant clinical improvement was observed, including a decrease in the number of painful joints, joint swelling, morning stiffness, and the PIP ring number.
These results suggest that this new topical NSAID prodrug may be useful in the treatment of rheumatoid arthritis.
