Pharmacodynamic effects of ketoprofen on crevicular fluid prostanoids in adult periodontitis

Abstract

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 randomized, partially double-blind, controlled trial was conducted to evaluate the pharmacodynamic effects of the NSAID, ketoprofen (KTP), on gingival crevicular fluid (GCF) prostanoids. 42 subjects, ages 35-57 years, with moderate to advanced adult periodontitis were recruited and monitored for 22 days. On day 1, subjects were randomized for 1 of 5 treatments: i) 0.5% KTP gel; ii) 1.0% KTP gel; iii) 1.0% KTP alternate gel; iv) 2.0% KTP gel; v) 25 mg KTP capsule (positive control). Subjects applied 1 ml of gel topically to their gingiva or administered one capsule p.o., b.i.d. for 14.5 days. GCF samples 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-treatment). GCF levels of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) were determined using RIA, and expressed in ng/ml and % reduction from baseline (%Effect). Neither a significant difference among groups nor a dose response in % effect for either prostanoid was evident, both overall and among cohorts with elevated baseline mediator levels ([PGE2]>34 ng/ml; [LTB4]>300 ng/ml). When data were combined from all groups, significant (p<0.01) % reductions in GCF PGE2 were noted at 1 and 2 h post-dosing (29% and 24% respectively). In comparing topical versus systemic formulations, all topical formulations were as equipotent as systemic dosing in altering local prostaglandin levels despite lower KTP exposures with gel treatments. These data indicate that both topical and systemic KTP therapies pharmacodynamically reduce GCF PGE2 levels in adult periodontitis subjects, allowing for potential inhibition of disease progression.

Evaluation of digital optical density of bone repair in rats medicated with ketoprofen

“…The authors observed that the administration of higher doses of this drug yielded a reduction of the area of cancellous bone and an increase in bone trabeculae. Paquette et al (2) evaluated the The results of the present study do not agree with those of the above-mentioned investigations (2,4,20). Unlike these authors, we have observed that the dosage and period of administration of a NSAID directly interfered with its mechanism of action because OD values of the unicortical bone defects created in tibiae of rats increased in both ketoprofen-treated (daily oral dose of 12.5 mg/kg for 30 days) and control groups up to the 21st day, with greater OD values for the ketoprofen group.…”

“…Non-steroidal anti-inflammatory drugs (NSAIDs) are competitive inhibitors of the cyclooxygenase enzyme (COX), which is in charge of the biosynthesis of prostaglandins and thromboxanes from the arachidonic acid (1)(2)(3). Two forms of the cyclooxygenase enzyme have been described, COX-1 and COX-2.…”

“…Current studies have associated the intake of NSAIDs with bone repair process (2,4,5) and have demonstrated that bone is one of the few tissues with remodeling capacity, being able to recover its structure and function even after a trauma. Direct digital radiography has been largely used in studies investigating bone defects because this methodology is as efficient as conventional radiographic techniques for detection of incipient bone lesions and offers technical resources and tools (softwares) that assist in visualization, delimitation and measurement of these lesions (6,7).…”

Protective effect of ketoprofen lysine salt on interleukin-1β and bradykinin induced inflammatory changes in hamster cheek pouch microcirculation

“…The ability of KLS to modulate the bronchoconstriction induced by BK and to a larger extent the increase in airway permeability induced by BK has been reported to depend on cyclooxygenase blockade [16]. In this regard, topical ketoprofen has been recently shown to reduce gingival crevicular fluid prostaglandin E 2 levels in adult periodontitis [17] and to reduce the rate of alveolar bone loss in monkeys with ligature-induced oral inflammation [18].…”

Short-Term effect of COX-2 selective inhibitor as an adjunct for the treatment of periodontal disease: a clinical double-blind study in humans

“…Regarding NSAID efficacy period, it has been shown that the inhibitory effect of PGE 2 continues only during drug intake phase and will end after drug therapy cessation (13). In this short-term evaluation, PD and BOP presented significant improvement during the observation period.…”