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In vitro and in vivo study of poly(ethylene glycol) conjugated ketoprofen to extend the duration of action

Authors
Choi, Hoo-KyunChun, Myung-KwanLee, Se HeeJang, Mee HeeKim, Hee DooJung, Chun SikOh, Seaung Youl
Issue Date
Aug-2007
Publisher
ELSEVIER SCIENCE BV
Keywords
ketoprofen; poly(ethylene glycol); conjugation; analgesic; anti-inflammatory
Citation
INTERNATIONAL JOURNAL OF PHARMACEUTICS, v.341, no.1-2, pp.50 - 57
Journal Title
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume
341
Number
1-2
Start Page
50
End Page
57
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/14643
DOI
10.1016/j.ijpharm.2007.03.045
ISSN
0378-5173
Abstract
Ketoprofen-polyethylene glycol (PEG) conjugates (KPEG) were prepared and their potential as a prolonged release system was investigated. Three KPEG conjugates were synthesized from ketoprofen and methoxy PEG with three different molecular weights by esterification in the presence of DCC. The KPEG conjugates were characterized by FT-IR and H-1 NMR spectroscopy. The rate of hydrolysis profile showed a specific acid-base catalysis pattern with a minimum at pH 4-5. The pharmacokinetic study after the intravenous and intramuscular administration of KPEG750 showed that the plasma levels of KP increased slowly and reached a maximum concentration at later time. The AUC of KPEG750 was higher than that after administering an equivalent dose of ketoprofen except 40 mg/kg dose of intramuscular administration. The tail-flick experiment and paw edema test after intramuscular administration showed that KPEG750 had extended analgesic and anti-inflammatory effects compared with ketoprofen. These results suggest that KPEG could be a promising NSAID prodrug with an extended pharmacological effect owing to delayed-release of parent drug. (c) 2007 Elsevier B.V. All rights reserved.
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