Pharmacodynamic effects of ketoprofen on crevicular fluid prostanoids in adult periodontitis

The reported therapeutic benefits of nonsteroidal anti-inflammatory drugs ( NSAIDs) in slowing periodontal disease progression appear intimately linked to the effective inhibition of local prostaglandin synthesis. This randomi zed, partially double-blind, controlled trial was conducted to evaluate the pharmacodynamic effects of the NSAID, ketoprofen (KTP), on gingival crevic ular fluid (GCF) prostanoids. 42 subjects, ages 35-57 years, with moderate to advanced adult periodontitis were recruited and monitored for 22 days. O n day 1, subjects were randomized for 1 of 5 treatments: i) 0.5% KTP gel; i i) 1.0% KTP gel; iii) 1.0% KTP alternate gel, iv) 2.0% KTP gel; v) 25 mg KT P capsule (positive control). Subjects applied 1 mi of gel topically to the ir gingiva or administered one capsule p.o, b.i.d. for 14.5 days. GCF sampl es were collected from posterior, interproximal sites on days 1 (pre-dosing ; 1. 2, 3, 6 h), 8 (pre-dosing; 2 h), 15 (pre dosing; 2 h) and 22 (post-tre atment). GCF levels of prostaglandin E-2 (PGE(2)) and leukotriene B-4 (LTB4 ) were determined using RIA, and expressed in ng/ml and % reduction from ba seline (%Effect). Neither a significant difference among groups nor a dose response in % effect for either prostanoid was evident, both overall and am ong cohorts with elevated baseline mediator levels ([PGE(2)]>34 ng/ml; [LTB 4]>300 ng/ml). When data were combined from all groups, significant (p<0.01 ) % reductions in GCF PGE(2) were noted at 1 and 2 h post-dosing (29% and 2 4%, respectively). In comparing topical versus systemic formulations, all t opical formulations were as equipotent as systemic dosing in altering local prostaglandin levels despite lower KTP exposures with gel treatments. Thes e data indicate that both topical and systemic KTP therapies pharmacodynami cally reduce GCF PGE levels in adult periodontitis subjects, allowing for p otential inhibition of disease progression.