title: In vitro and in vivo study of poly(ethylene glycol) conjugated ketoprofen to extend the duration of action.
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 (1)H 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 40mg/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.
authors.affiliation: BK21 Project Team, School of Pharmacy, Chosun University, 375 Seosuk-dong, Dong-gu, Gwangju 501-759, Republic of Korea.
authors.forename: Hoo-Kyun
authors.initials: HK
authors.lastname: Choi
authors.forename: Myung-Kwan
authors.initials: MK
authors.lastname: Chun
authors.forename: Se Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Mee Hee
authors.initials: MH
authors.lastname: Jang
authors.forename: Hee Doo
authors.initials: HD
authors.lastname: Kim
authors.forename: Chun Sik
authors.initials: CS
authors.lastname: Jung
authors.forename: Seaung Youl
authors.initials: SY
authors.lastname: Oh
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D002351:Carrageenan; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004024:Dicyclohexylcarbodiimide / Q000737:chemistry; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007660:Ketoprofen / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008970:Molecular Weight; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry*; D011355:Prodrugs / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011355:Prodrugs; D011092:Polyethylene Glycols; D004024:Dicyclohexylcarbodiimide; D002351:Carrageenan; C028210:monomethoxypolyethylene glycol; D007660:Ketoprofen