Comparative assessment of effectiveness of ketoprofen and ketoprofen/beta-cyclodextrin complex in two experimental models of inflammation in rats.
Oral administration of non-steroidal anti-inflammatory drugs (NSAIDs) can lead to adverse effects such as gastrointestinal distress. The complexation of different groups of active substances with β-cyclodextrin (β-CD) has drawn considerable interest over recent years. The purpose of this study was to analyze the ketoprofen/β-cyclodextrin (K/β-CD) conjugate complex as well as to assess its anti-inflammatory effect after oral administration (doses of 30 mg/m(2) and 15 mg/m(2) of body surface), compared with ketoprofen. The studies were done on two models of experimentally-induced acute inflammation in rats (n = 48, 6/group), by means of intraplantar administration of a 10% aqueous kaolin suspension and intraperitoneal administration of a 1% sodium thioglycolate solution. The dynamics of the acute inflammatory process and the anti-inflammatory effects were monitored using plethysmometric determinations after 3, 6, 9, 12, 24 and 48 h (plantar inflammation), and the absorbance of the exudates (spectrophotometrically read) and nucleated cell counts after 24 h (peritoneal inflammation). The coupling of ketoprofen with β-CD resulted in increased solubility (100% in 60 min) of the newly-formed product, which further resulted in a higher bioavailability compared with ketoprofen (<40% in 120 min). In both models of experimentally-induced inflammation, the K/β-CD complex had a higher anti-inflammatory activity than ketoprofen.
Department of Pharmacology, University of Agricultural Sciences and Veterinary Medicine, Lasi, Romania.
Mariana
M
Grecu
Valentin
V
Năstasă
Cornelia
C
Ilie
Liviu
L
Miron
Mihai
M
Mareş
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001682:Biological Availability; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000662:veterinary*; D007660:Ketoprofen / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D010991:Plethysmography / Q000662:veterinary; D051381:Rats; D017208:Rats, Wistar; D012376:Rodent Diseases / Q000139:chemically induced / Q000188:drug therapy*; D064449:Sequestering Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D013047:Specific Pathogen-Free Organisms; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D064449:Sequestering Agents; D047392:beta-Cyclodextrins; D007660:Ketoprofen; C031215:betadex
bioavailability; inclusion complex; non-steroidal anti-inflammatory drugs; propionic acid derivatives; rodent model