Pharmacokinetics and pharmacodynamics of ketoprofen plasters

Ketoprofen plasters of 70 cm² size using DuroTak® acrylic adhesive polymers were developed either containing 30 mg (Ketotop-L) or 60 mg drug (Ketotop-P). The in vitro skin permeation profile was obtained in hairless mouse skin and showed the permeation rate of Ketotop-P to be twice that of Ketotop-L. The plasma concentration profile of ketoprofen was determined in Sprague-Dawley rats after applying a 3 × 3 cm² plaster. AUC_0-24h and C_max of Ketotop-P were 260.92 μg · h/ml and 25.09 μg/ml, respectively, which were about twice the values of Ketotop-L. The hind paw edema induced by carrageenan injection was measured for 6 h after applying a 2 × 2 cm² plaster, and the area under the time-response curve (AUR) value was significantly lower in Ketotop-P attached rats (180.70% · h) than in those with the Ketotop-L (298.65% · h) and the control (407.04% · h) groups, indicating a stronger anti-inflammatory action of Ketotop-P. However, the analgesic effect of the two formulations did not show a statistically significant difference. In conclusion, Ketotop-P was able to achieve higher plasma concentration of ketoprofen, thereby exhibiting higher and more constant anti-inflammatory effect compared with Ketotop-L.