Action of Ketoprofen on Hepatic Lysosome in the Rat

Migne, J; Y, Vedrine; Bourat, G; Fournel, J; Heusse, D

doi:10.1093/rheumatology/15.5.15

Cited by 11 publications

(8 citation statements)

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“…Alternatively, the changes in PGE 2 and LTB 4 recorded here may represent regression of the periodontitis lesion to one of gingivitis (i.e., predominated by polymorphonuclear leukocytes) (Offenbacher 1996). The observed elevations in LTB 4 contradict previous reports that ketoprofen reduces lipoxygenase metabolites in vitro and in primates with ligature-induced periodontitis (Migne et al 1976, Li et al 1996. Again, differences in study design or GCF sampling protocols may account for the discord in pharmacodynamic responses observed between animal models and the present human trial.…”

Section: Discussionsupporting

confidence: 62%

“…Most NSAIDs like ibuprofen inhibit both isoforms of cyclooxygenase. One NSAID, ketoprofen, has appeared distinctive in its reputed ability to depress lipoxygenase products like LTB 4 in vitro and in vivo (Migne et al 1976, Li et al 1996.…”

Section: Discussionmentioning

confidence: 99%

“…Whereas apparent inhibitory concentrations (IC50) for ibuprofen, naproxen, meclofenamate, flurbiprofen and indomethacin range from 10-1500 nM, the IC50 value for ketoprofen averages 5.4 nM. Other in vitro anti-inflammatory effects of ketoprofen include anti-bradykinin activity, stabilization of lysosomal membranes, reputed inhibition of leukotriene release from activated cells, and suppression of leukocyte migration (Meacock and Kitchen 1976, Julou et al 1976, Migne et al 1976, Smith 1978, Walker 1984. Recently, we documented significant reductions in crevicular prostanoids (PGE 2 and LTB 4 ) and alveolar bone loss in periodontally diseased monkeys treated with topical 1.0% ketoprofen creams over a sixmonth dosing period versus placebo controls (Li et al 1996).…”

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confidence: 99%

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Pharmacodynamic effects of ketoprofen on crevicular fluid prostanoids in adult periodontitis

Paquette

Lawrence

McCombs

et al. 2000

J Clinic Periodontology

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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.

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Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Pharmacodynamic effects of ketoprofen on crevicular fluid prostanoids in adult periodontitis

Paquette

Lawrence

McCombs

et al. 2000

J Clinic Periodontology

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“…Fossgreen 1976, Offenbacher et al 1990). Other, unique anti-inflatnmatory effects of ketoprofen include its anti-bradykinin activity, stabilization of Iysosomal membranes, reputed inhibition of leukotriene release from activated cells, and suppression of leukocyte migration (Meacock & Kitchen 1976, Migne et al 1976, Smith 1978, Walker 1984. Interestingly, these drug actions appear to be enantioseiective and restricted to the (S)-enantiomer (Jamali et al 1989).…”

mentioning

confidence: 99%

Enantiospecific inhibition of ligature‐induced periodontitis in beagles with topical (S)‐ketoprofen

Paquette

Fiorellini

Martuscelli

et al. 1997

J Clinic Periodontology

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Systemic and topical administration of non-steroidal anti-inflammatory drugs (NSAIDs) has been shown to reduce periodontal disease progression in both animal models and human subjects. Our present research focuses on single enantiomers of these agents to examine whether enantiospecific therapy will be efficacious in slowing periodontitis. The purpose of this study was to evaluate the inhibitory effects of (S)-ketoprofen on experimentally induced alveolar bone loss in beagle dogs. 16, 18-month-old, female beagles were brought to optimal periodontal health over a 2-week pretreatment period. Experimental periodontitis was then induced by placing silk ligatures around premolar and molar teeth and by instituting a soft, plaque-promoting diet. At baseline, animals were randomized to 1 of 4 groups, consisting of 2x daily administration of (1) placebo dentifrice, (2) 0.3% (S)-ketoprofen dentifrice, (3) 3.0% (S)-ketoprofen dentifrice, or (4) 10.0 mg (S)-ketoprofen capsules (p.o.) over a 60 day treatment period. Standardized, periapical radiographs exposed at days 1 and 60 were analyzed by computer-assisted digital radiography in order to assess the rate of alveolar bone loss. Secondary outcomes included technetium 99m-tin-diphosphonate (99mTc-Sn-MDP) uptake and the gingival index. At baseline, no differences were observed among the groups for linear bone height or 99mTc-Sn-MDP uptake ratios. From days 1 to 60, cohorts differed significantly in terms of bone loss rates (p < 0.001). In particular, beagles treated with systemic or topical (S)-ketoprofen (0.3% or 3.0% dentifrices) exhibited significantly lower mean rates of bone loss compared to placebo treated beagles (p < 0.05). Group differences in mean radiopharmaceutical uptake ratio changes approached significance (ANOVA, p = 0.07), where animals treated with topical 0.3% (S)-ketoprofen demonstrated a reduction and other groups demonstrated elevations over the 60-day dosing period. Treatment cohorts did differ significantly with respect to changes in mean gingival indices (p < 0.05). Animals treated with 0.3% or 3.0% (S)-ketoprofen dentifrice exhibited significantly reduced elevations in gingival index scores as compared to placebo treated animals. These data provide evidence that enantiospecific therapy with (S)-ketoprofen, topically or systemically delivered, may alter the progression of periodontal disease in the beagle dog model.

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“…Its mode of action appears to be similar to that qf other NSAIDs and includes inhibition of prostaglandin and leukotriene biosynthesis, antibradykinin activity, and lysosome membrane-stabilizing activity. 2,3 Ketoprofen has been studied in humans both as an antirheumatic and as an analgesic. Our summary focuses on five independent studies (three of which we performed) that were done to evaluate the analgesic efficacy of ketoprofen in three different pain models: postpartum, general surgery, and chronic cancer pain.…”

mentioning

confidence: 99%

Analgesic Efficacy of Ketoprofen in Postpartum, General Surgery, and Chronic Cancer Pain

Sunshine¹,

Olson²

1988

The Journal of Clinical Pharma

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Action of Ketoprofen on Hepatic Lysosome in the Rat

Cited by 11 publications

References 0 publications

Pharmacodynamic effects of ketoprofen on crevicular fluid prostanoids in adult periodontitis

Pharmacodynamic effects of ketoprofen on crevicular fluid prostanoids in adult periodontitis

Enantiospecific inhibition of ligature‐induced periodontitis in beagles with topical (S)‐ketoprofen

Analgesic Efficacy of Ketoprofen in Postpartum, General Surgery, and Chronic Cancer Pain

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