Pharmacokinetics and pharmacodynamics of ketoprofen plasters.
Ketoprofen plasters of 70 cm(2) 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 x 3 cm(2) plaster. AUC(0-24h) and C(max) of Ketotop-P were 260.92 microg.h/ml and 25.09 microg/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 x 2 cm(2) 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.
Heo
Sung-Koun
SK
College of Pharmacy, Pusan National University, Busan 609-735, Korea.
Cho
Jeiwon
J
Cheon
Ji-Woong
JW
Choi
Min-Koo
MK
Im
Dong-Soon
DS
Kim
Jung Ju
JJ
Choi
Yang Gyu
YG
Jeon
Do Yong
DY
Chung
Suk-Jae
SJ
Shim
Chang-Koo
CK
Kim
Dae-Duk
DD
D000180:Acrylic Resins / Q000737:chemistry; D000269:Adhesives / Q000737:chemistry; D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D019540:Area Under Curve; D002351:Carrageenan; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D006614:Hindlimb / Q000378:metabolism; D006358:Hot Temperature / Q000009:adverse effects; D066298:In Vitro Techniques; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control; D007660:Ketoprofen / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008812:Mice, Hairless; D010147:Pain Measurement / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption
D000180:Acrylic Resins; D000269:Adhesives; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002351:Carrageenan; D007660:Ketoprofen