BIOPHARMACEUTICS & DRUG DISPOSITION Biopharm. Drug Dispos. 29: 37–44 (2008) Published online in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/bdd.587 Pharmacokinetics and Pharmacodynamics of Ketoprofen Plasters Sung-Koun Heo a , Jeiwon Cho b , Ji-Woong Cheon c , Min-Koo Choi c , Dong-Soon Im a , Jung Ju Kim d , Yang Gyu Choi d , Do Yong Jeon e , Suk-Jae Chung c , Chang-Koo Shim c and Dae-Duk Kim c, * a College of Pharmacy, Pusan National University, Busan 609-735, Korea b Korea Institute of Science and Technology, Center for Neural Science, Seoul 130-650, Korea c College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Korea d Pharmaceutical Research Institute, AMOREPACIFIC Corporation/R & D Center, Gyeonggi-do 446-729, Korea e Pacificpharma Corporation, Seoul 140-871, Korea ABSTRACT: Ketoprofen plasters of 70 cm 2 size using DuroTak 1 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 cm 2 plaster. AUC 024h and C max of Ketotop-P were 260.92 mg  h/ml and 25.09 mg/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 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. Copyright # 2007 John Wiley & Sons, Ltd. Key words: ketoprofen; plaster; pharmacokinetics; pharmacodynamics; anti-inflammation; analgesic Introduction Ketoprofen [2-(3-benzoylphenyl) propionic acid] is a nonsteroidal anti-inflammatory drug (NSAID) used for the treatment of osteoarthritis and rheumatoid arthritis [1,2]. However, as in the case of most NSAIDs, oral ketoprofen formula- tions cause stomach irritation, hepatotoxicity and kidney failure [3,4]. Due to these adverse effects, the need for a non-oral delivery system of ketoprofen has been called for, and as a result, several topical forms of ketoprofen have been developed [5–7]. Topical application of keto- profen on the joints or muscles can increase the drug concentration at the target site as well as lower the concentration in the systemic circula- tion, thereby reducing stomach irritations and liver toxicity [8,9]. High levels of ketoprofen in intra-articular adipose tissue and in capsular tissue were observed in gel formulations [10]. Compared with when ketoprofen was admi- nistered orally at a 50 mg dose, a 30 mg plaster significantly decreased the plasma drug con- centration by 120 orders of magnitude while maintaining about a 4–7 times higher concentra- tion at the target sites (i.e. meniscus and *Correspondence to: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151- 742, Korea. E-mail: ddkim@snu.ac.kr Received 8 February 2007 Revised 3 July 2007 Accepted 28 August 2007 Copyright # 2007 John Wiley & Sons, Ltd.