Disease relevance of ZINC00005560

• Comparison of the efficacy and tolerability of dexketoprofen and ketoprofen in the treatment of primary dysmenorrhea [1].
• (S)-ketoprofen accumulation in premature neonates with renal failure who were exposed to the racemate during pregnancy [2].
• Photoallergic contact dermatitis from dexketoprofen: study of 6 cases [3].
• The purpose of this study was to evaluate the inhibitory effects of (S)-ketoprofen on experimentally induced alveolar bone loss in beagle dogs [4].
• Enantiospecific inhibition of ligature-induced periodontitis in beagles with topical (S)-ketoprofen [4].

High impact information on ZINC00005560

• The aim of this study was to investigate the HSA-mediated mechanism involved in the in vitro hydrolysis by albumin of the acyl glucuronides of (R)- and (S)-ketoprofen (a nonsteroidal anti-inflammatory drug), as model compounds [5].
• Clinical pharmacokinetics of dexketoprofen [6].
• Relative bioavailability of oral dexketoprofen (12.5 and 25mg, respectively) is similar to that of oral racemic ketoprofen (25 and 50mg, respectively), as measured in all cases by the area under the concentration-time curve values for (S)-(+)-ketoprofen [6].
• Repeated (5-day) oral administration of dexketoprofen as the trometamol salt causes less gastric ulceration than was observed after the acid form of both dexketoprofen and the racemate [7].
• Dexketoprofen-induced antinociception in animal models of acute pain: Synergy with morphine and paracetamol [8].

Biological context of ZINC00005560

• Changes in urodynamic parameters induced by LPS were prevented by doses of either dexketoprofen (1 mg kg(-1), i.v.) or NS-398 (2 mg kg(-1), i.v.) which were ineffective in control animals [9].
• 6. In sucrose gap experiments, (S)-ketoprofen (10-100 microM) produced a time-dependent shortening of spontaneous action potentials of the guinea-pig renal pelvis and reduced the amplitude and duration of the accompanying phasic contractions [10].
• 5. There was no difference between AUC for (R)- and (S)-ketoprofen for either unbound or total drug [11].
• IC50 values obtained for dexketoprofen, (-)-R-ketoprofen, and rac-ketoprofen were 3.5 microM, 45.3 microM, and 5.8 microM, respectively [12].
• A new (S)-ketoprofen specific esterase (EST-Y29) was identified from a metagenome library from environmental samples, which showed homologies with class C-beta lactamase, penicillin binding protein, and other lipases/esterases [13].

Anatomical context of ZINC00005560

• 4. In the guinea-pig isolated ureter, phasic contractions were induced by EFS (5 ms pulse width, 60 V): (S)-ketoprofen (100-500 microM) had no effect on the EFS-evoked contractions [10].
• The absorption ratios of (R)- and (S)-ketoprofen for the absorption process from the gastrointestinal tract into the systemic circulation were 87.0% and 83.8%, respectively [14].
• In liver homogenates or subcellular fractions, the enantiomer (S)-ketoprofen (S-KP) was recovered unchanged, whereas (R)-ketoprofen (R-KP) was partially converted into its Coenzyme A (CoA) thioester and inverted to S-KP [15].
• Thus, the safety indexes (UD50/ED50) of the stomach (or small intestine) for M-5011, IND, KP, DIF, TIA and ZLT were 140.05 (73.16), 42.67 (22.76), 71.57 (38.39), 6.16 (3.29), 13.15 (9.74) and 6.60 (3.26), respectively [16].
• These results correlated with those obtained in the study of racemic ketoprofen and its enantiomers on cyclooxygenase activity of rat brain microsomes, where dexketoprofen also inhibited enzymatic activity stereoselectively [12].

Associations of ZINC00005560 with other chemical compounds

• When contraction of the ureter was evoked by 80 mM KCl, indomethacin produced about 30 and 80% inhibition at 100 and 300 microM, respectively, while (S)-ketoprofen (300 microM) was ineffective [10].
• Significant levels of prostaglandin F2 alpha (PGF2 alpha) were synthesized in rat brain fragments after 10 min of incubation at 37 degrees C. Dexketoprofen was found to be a potent inhibitor of this PGF2 alpha production in rat brain (IC50 = 6.2 nM), and it completely suppressed PGF2 alpha production at 1 microM concentration [12].
• By using such an immobilized enzyme as biocatalyst, the process for preparing enantiopure (S)-ketoprofen becomes simpler and more practical as compared with the previously reported procedures and the product was obtained with >94% ee at 22.3% conversion in the presence of an optimal concentration (0.5 mg/ml) of Tween-80 at pH 3 [17].
• Kinetic studies on the intramolecular acyl migration of beta-1-O-acyl glucuronides: application to the glucuronides of (R)- and (S)-ketoprofen, (R)- and (S)-hydroxy-ketoprofen metabolites, and tolmetin by 1H-NMR spectroscopy [18].
• Odds ratios for a decrease in pain score of at least 1 from baseline (on the 11 point scale) when given dexketoprofen rather than diclofenac at 15, 30, 45, and 60 minutes were; 2.66 (1.19 to 5.98), 3.52 (1.60 to 7.73), 4.48 (1.72 to 11.65), and 5.54 (1.90 to 16.15) [19].

Gene context of ZINC00005560

• The present work evaluates the effects of the COX-1/COX-2 inhibitor dexketoprofen as well as of a selective COX-2 inhibitor, NS-398, on urodynamic function following endotoxin (LPS) or cyclophosphamide (CYP)-induced inflammation of the urinary bladder [9].
• S(+)-ketoprofen (dexketoprofen) stereoselectively inhibits cyclooxygenase (COX) in vitro but very little is known about the differential activity of ketoprofen enantiomers in vivo [20].
• 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 [4].
• A biotransformation process was developed for the production of (S)-ketoprofen by enantioselective hydrolysis of racemic ketoprofen ester using the mutant Trichosporon laibacchii strain CBS 5791 [21].

Analytical, diagnostic and therapeutic context of ZINC00005560

• The spinal injection of (S)-ketoprofen alone or of morphine alone did not produce antiallodynic activity [22].
• Plasma dexketoprofen concentrotions were determined by HPLC and the main outcome measures were area under curve of concentration vs. time (AUC0-infinity), maximal plasma concentration (Cmax), and time to reach maximal concentration (t(max)) [23].
• Determination of (R)- and (S)-ketoprofen in human plasma by liquid chromatography/tandem mass spectrometry following automated solid-phase extraction in the 96-well format [24].
• Effect of perioperative administration of dexketoprofen on opioid requirements and inflammatory response following elective hip arthroplasty [25].
• Sedation scores were less (P=0.03) in group D. CONCLUSIONS: Perioperative administration of dexketoprofen 25 mg 8 hourly markedly improves analgesia and decreases opioid requirements (and associated adverse effects) following hip arthroplasty [25].

References