Disease relevance of Profenid

• Ketoprofen causing pseudotumor cerebri in Bartter's syndrome [1].
• This high-risk association between MTX toxicity and ketoprofen may also apply to other non-steroidal anti-inflammatory drugs [2].
• Life-threatening asthma, urticaria, and angiooedema after ketoprofen [3].
• Conjunctivitis due to ketoprofen [4].
• Interferon-alpha 2b combined with daily ketoprofen administration improves virological response in chronic hepatitis C: a prospective and randomised trial [5].

Psychiatry related information on Profenid

• This stereoselectivity could vary with experimental conditions, in particular with protein concentration (ketoprofen, etodolac), leading to individual differences [6].
• 1,3-Diacetyl-2-ketoprofen glyceride (DAKG), a prodrug of ketoprofen, was synthesized as a model compound in our attempt to develop a central nervous system (CNS) drug delivery system to treat Alzheimer's disease [7].
• The composition of a polymeric potential-determining phase for ketoprofen selective electrode has been determined and the following basic electrode parameters were examined: measurement range, slope characteristic, limit of detection, response time, lifetime and selectivity coefficients in relation to some organic and inorganic anions [8].
• Intravenously, only ketoprofen and tolfenamic acid raised the pain thresholds [9].

High impact information on Profenid

• All the other NSAIDs with sufficient data for individual analysis (ibuprofen, naproxen, diclofenac, ketoprofen, and indomethacin) had relative risks similar to that for overall NSAID use [10].
• There were no abnormalities in MTX kinetics or evidence of MTX toxicity when ketoprofen was given at least 12 h after completion of high-dose MTX infusion [2].
• The COX-1 inhibitors ketoprofen and SC560 failed to inhibit the HGF/SF-induced angiogenic events in vitro and in vivo [11].
• Ketoprofen, a nonspecific COX inhibitor, and SC-236 had no effect on the NOS2 pathway [12].
• Indomethacin, flurbiprofen, and ketoprofen, inhibitors of PGHS activity containing a free carboxylic acid group, do not exhibit any inhibitory effects against the activity of PGHS-1(Arg120-->Glu) [13].

Chemical compound and disease context of Profenid

• The analgesic efficacy and safety of dexketoprofen trometamol (the active enantiomer of the racemic compound ketoprofen) (25mg q.i.d.) vs. ketorolac (10mg q.i.d.) was assessed in 115 patients with bone cancer pain included in a multicenter, randomized, double-blind, parallel group study [14].
• The efficacy of intramuscular tiaprofenic acid (TA) was investigated in 3 separate studies: a multicentre open study involving 487 patients with various rheumatic conditions: an open study of 31 patients with active osteoarthritis of the knee; and an open comparative study with ketoprofen involving 30 patients with acute gout [15].
• In each model of pleurisies, ketoprofen and indomethacin reduced the volume of exudate and leukocyte count in a dose-dependent manner but ketoprofen was more active than indomethacin [16].
• Age-related reporting analysis suggests a higher toxicity for diclofenac and piroxicam in the elderly compared with nimesulide and ketoprofen [17].
• Aspirin, ibuprofen, indomethacin, ketoprofen, flurbiprofen, phenylbutazone, naproxen, prednisolone, and penicillamine did not increase ALA synthase activity and should be safe in porphyria [18].

Biological context of Profenid

• Overall, these studies have shown that sucralfate does not alter the pharmacokinetics of naproxen and ketoprofen; the amount of drug absorbed remains constant [19].
• Food caused a significant decrease in the bioavailability of ketoprofen (over 40 percent) following both single-dose (23.8 versus 13.1 micrograms.hour/ml) and multiple-dose (29.3 versus 16.8 micrograms.hour/ml) administration [19].
• Probenecid decreased protein binding of ketoprofen by 28 +/- 7%, total ketoprofen clearance by 67 +/- 11%, clearance of unbound ketoprofen by 74 +/- 10%, clearance of unbound ketoprofen by conjugation by 91 +/- 5%, and renal clearance of ketoprofen conjugates by 93 +/- 4% [20].
• An alternative explanation to inhibition of conjugation involves cumulation and subsequent hydrolysis of ketoprofen conjugates as a result of the renal action of probenecid [20].
• The AUC for total ketoprofen was greater in serum than in synovial fluid [21].

Anatomical context of Profenid

• Furthermore, the differential response to ketoprofen indicates that the specific antigen-stimulated mediator release profiles of dermal and synovial mast cells are different [22].
• Total and free ketoprofen in serum and synovial fluid after intramuscular injection [21].
• Immunoblots of liver microsomes incubated with ketoprofen acylglucuronide and probed with antiketoprofen antibodies revealed the presence of several protein adducts; among those was a major immunoreactive protein at 56 kDa, in the range of the apparent molecular mass of UGTs [23].
• Addition of ketoprofen in vitro to B cells from patients with CVI resulted in improved proliferation and differentiation in four of five additional patients with CVI studied [24].
• The presence of these covalent adducts within the endoplasmic reticulum of cells expressing UGT2B1 was demonstrated following addition of ketoprofen to culture medium by immunofluorescence microscopy with antiketoprofen antibodies [23].

Associations of Profenid with other chemical compounds

• Of the NSAIDs in common use, ibuprofen and diclofenac were found to be associated with the lowest relative risk; indomethacin, naproxen, sulindac, and aspirin were associated with intermediate risk; and azapropazone, tolmetin, ketoprofen, and piroxicam were associated with higher risk [25].
• Finally, UGT purification from rat liver microsomes incubated with ketoprofen glucuronide led to the isolation of UGT adducts recognized by both anti-UGT and antiketoprofen antibodies, providing strong evidence that UGTs are targets of this metabolite [23].
• Vial liquid-phase microextraction (LPME) combined with capillary electrophoresis (CE) was evaluated for the determination of the acidic drugs ibuprofen, naproxen, and ketoprofen present in water samples and in human urine [26].
• In humans, the relative bioavailability of oral dexketoprofen trometamol (12.5 and 25 mg, respectively) is similar to that of oral racemic ketoprofen (25 and 50 mg, respectively), as measured in all cases by the area under the concentration-time curve values for S(+)-ketoprofen [27].
• Ketorolac 10 and 20 mg, ketoprofen 50 mg and placebo were compared in a multiple-dose, double-blind, randomized analgesic study that included 150 patients with pain after impacted third molar removal [28].

Gene context of Profenid

• (S)oxazepam glucuronidation is inhibited by ketoprofen and other substrates of UGT2B7 [29].
• Therefore, we studied the interaction of the ketoprofen metabolites with the COX enzymes [30].
• Either M-5011 or ketoprofen potently inhibited prostaglandin (PG) E2 production by cyclooxygenase (COX)-2 from exogenous AA in interleukin-1beta (IL-1beta)-stimulated cells [31].
• 4. Under these experimental conditions, ketoprofen enantioselectively inhibited the cyclo-oxygenase activity of both PGHS-1 and PGHS-2 with equal potency (IC50 ratio: approx. 0.5 for both enantiomers), while L-745,337 and NS-398 achieved selective inhibition of monocyte PGHS-2 (IC50 ratio: > 150) [32].
• 4. A cyclo-oxygenase inhibitor, ketoprofen (3 mg kg-1) administered 15 min before either cytokine completely abolished the fever induced by both IL-1 alpha (2500 u kg-1) and IL-1 beta (500 u kg-1) [33].

Analytical, diagnostic and therapeutic context of Profenid

• A dose response was observed between the two doses of ketoprofen, with the 100 mg dose providing significantly greater analgesia over the lower dose [34].
• Ketoprofen was assayed by HPLC [21].
• When six normal men took probenecid with ketoprofen in a two-treatment crossover study, steady-state plasma concentrations of ketoprofen and ketoprofen conjugates rose, but plasma protein binding of ketoprofen and urinary excretion of ketoprofen conjugates decreased [20].
• Serum concentrations of ketoprofen were measured by high pressure liquid chromatography [35].
• CONCLUSION: Absorption of ketoprofen after rectal administration is reasonably rapid and predictable [36].

References