title: The effect of ketoprofen creams on periodontal disease in rhesus monkeys.
abstract: Ketoprofen creams were evaluated for the treatment of periodontal disease in a placebo-controlled, double-blind study in the rhesus monkeys, Macaca mulatta. Two formulations containing ketoprofen (1%), with or without vitamin E, were evaluated against appropriate controls (8 monkeys per group). Two weeks prior to treatment, the animals received prophylaxis on only the left side of the mouth (spontaneous model). Selected teeth on the right side of the mouth were ligated (ligature model). The creams were administered to the gingiva once daily at a standard dose of 1.8 ml per monkey for 6 months. Clinical assessments were made 2 wk before initiation, at baseline and 1, 2, 3 and 6 months post-treatment. The clinical parameters included plaque formation, gingival redness, edema, bleeding on probing and Ramfjord Attachment Level measurements (RAL). Radiographs were taken at 2 wk before initiation, baseline and at 3 and 6 months post-treatment. Digital, subtraction radiography was used to measure vertical linear bone loss along the interproximal root surfaces of the left and right mandibular first molars. Gingival crevicular fluid (GCF) was collected for biochemical assays on PGE2, TxB2, LTB4, IL-1 beta and TNF alpha. There were no significant differences among groups with respect to gingival indices. Radiographic data demonstrated significant positive effects on bone activity in both groups treated with ketoprofen formulations with improvement over time in the ligature model (0.01 < or = p < or = 0.04). The placebo group exhibited bone loss of 1.96 +/- 0.48 and 1.40 +/- 0.56 mm per site at 3 and 6 months, respectively. The group treated with ketoprofen cream showed an apparent bone gain of 0.28 +/- 0.41 and 0.78 +/- 0.47 mm per site at 3 and 6 months, respectively. The group treated with ketoprofen cream containing vitamin E showed a mean bone loss of 0.41-0.48 mm per site at 3 months with improvement to an apparent bone gain of 0.31 +/- 0.44 mm per site at 6 months. The biochemical data demonstrated early and significant suppression of GCF-LTB4 by both ketoprofen formulations at 1 month, which preceded the significant suppression of GCF-PGE2 at 2 and 3 months in the ligature model (p < 0.003) and at 2 to 6 months in the spontaneous model (p < 0.02). We conclude that ketoprofen at 1% level in suitable topical vehicles can effectively inhibit GCF-LTB4 and GCF-PGE2 and positively alter alveolar bone activity in the ligature-induced model of periodontitis in the monkey.
authors.affiliation: Block Drug Company, Inc., Jersey City, NJ, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Li
authors.forename: R
authors.initials: R
authors.lastname: Vogel
authors.forename: M K
authors.initials: MK
authors.lastname: Jeffcoat
authors.forename: M C
authors.initials: MC
authors.lastname: Alfano
authors.forename: M A
authors.initials: MA
authors.lastname: Smith
authors.forename: J G
authors.initials: JG
authors.lastname: Collins
authors.forename: S
authors.initials: S
authors.lastname: Offenbacher
mesh_terms: D000287:Administration, Topical; D016301:Alveolar Bone Loss / Q000000981:diagnostic imaging / Q000209:etiology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D003773:Dental Plaque / Q000209:etiology; D015232:Dinoprostone / Q000032:analysis / Q000037:antagonists & inhibitors; D004311:Double-Blind Method; D004487:Edema / Q000209:etiology; D004643:Emollients; D005260:Female; D005500:Follow-Up Studies; D005883:Gingival Crevicular Fluid / Q000737:chemistry; D005884:Gingival Hemorrhage / Q000209:etiology; D005891:Gingivitis / Q000209:etiology; D007375:Interleukin-1 / Q000032:analysis; D007660:Ketoprofen / Q000008:administration & dosage / Q000627:therapeutic use*; D007975:Leukotriene B4 / Q000032:analysis / Q000037:antagonists & inhibitors; D008253:Macaca mulatta; D008297:Male; D008963:Molar; D017622:Periodontal Attachment Loss / Q000209:etiology; D010518:Periodontitis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D010919:Placebos; D011856:Radiographic Image Enhancement; D011897:Random Allocation; D013382:Subtraction Technique; D013929:Thromboxane B2 / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014810:Vitamin E / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004643:Emollients; D007375:Interleukin-1; D010919:Placebos; D014409:Tumor Necrosis Factor-alpha; D014810:Vitamin E; D007975:Leukotriene B4; D013929:Thromboxane B2; D007660:Ketoprofen; D015232:Dinoprostone