• Journal of Pharmaceutical Investigation
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• v.12 no.2
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• pp.37-44
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• 1982

In order to enhance water solubility, ketoprofen was made as lysine salt, such as acetylsalicylic acid lysine salt, ibuprofen lysine salt and amino acid salt of phenylbutazone. The purpose of this study was to make a comparison between ketoprofen lysine salt in aspects of analgesic, anti-inflammatory, and antipyretic effect. The experimental results were summerized as followings. 1. Ketoprofen lysinate was composed of one molecule of ketoprofen and one molecule of lysine. The product was water soluble and melting point was $92^{\circ}C{\sim}94^{\circ}C$. 2. Ketoprofen lysinate showed about 2 times stronger analgesic effect than that of ketoprofen while no difference in antipyretic effect was observed. 3. $LD_{50}$ of ketoprofen lysinate was higher than that of ketoprofen, suggesting ketoprofen lysinate as safer drug. 4. Blood concentration of ketoprofen lysinate was $156{\mu}g/ml$ while the concentration of ketoprofen was $116{\mu}g/ml$ in 30 min., suggesting long acting as well as high blood concentration.

• Journal of Pharmaceutical Investigation
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• v.13 no.2
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• pp.66-72
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• 1983

Ketoprofen, 2-(3-benzoyl phenyl) propionic acid, has many advantages over the other antiinflammatory drugs, such as salicylates, phenytbutazone, and indomethacin. According to the reports, ketoprofen is well tolerated by patients and has very low incidence of side effects and toxic reactions. Although ketoprofen is widely used as an antiinflammatory agent, it shows poor solubility in water. In order to enhance water solubility, ketoprofen was made as lysine salt, such as acetylsalicylate lysine salt, ibuprofen lysine salt and amino acid salt of phenylbuatzone. The purpose of this study was to compare with ketoprofen lysinate in aspect of binding to human serum albumin (HSA) were made, and the association constant and the number of binding site were obtained using difference spectrophotometry. The number of binding site of HSA for ketoprofen and ketoprofen lysinate appears to be 3.3,3.2 respectively and association constants were found as follow; HSA-ketoprofen $2.23{\times}10^4\;M^{-1}$, HSA-ketoprofen lysinate $1.02{\times}10^4\;M^{-1}$.

• Journal of Veterinary Clinics
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• v.16 no.1
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• pp.193-198
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• 1999

Ketoprofen has been used as nonsteroidal anti-inflammatory (NSAI) agent for analgesia in surgical patients and increasing numbers of surgical patients are chronically take some forms of NSAI drugs. The purpose of this study was to investigate the therapeutic effects of ketoprofen on the healing of a closed linear surgical wound and on the contraction of an opened surgical wound in rats. The experimental groups were divided into two groups and ten rats were allocated in each group. In ketoprofen-treated group, the rats were given 2.5 mg/mg/day of ketoprofen by s.c. for ten days. In control group, the rats were given 1ml of benzyl alcohol and distilled water by s.c. for ten days. After time period, all rats were sacrificed, and the breaking strength and the collagen concentrations, at the wound site, were measured. In ketoprofen-treated group, the mean breaking strength and the mean collagen concentration were significantly decreased when compared with those of controls. The ketoprofen-treated group had shown a mean rate of wound contraction less than that of the control, although not statistically significant. These results suggested that ketoprofen impaired wound healing.

• KSBB Journal
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• v.25 no.3
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• pp.297-302
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• 2010

Ketoprofen is one of the propionic acid class of nonsteroidal anti-inflammatory drug with analgesic and antipyretic effects. The most common side effects from ketoprofen after oral administration are gastrointestinal irritation, diarrhea, abdominal pain and retention of fluid. Ketoprofen was formulated as water-soluble gels to reduce these side effects. To increase the skin permeability of ketoprofen, microsphere containing ketoprofen was prepared with chitosan and ploy-$\varepsilon$-caprolactone. And then prepared microsphere was manufactured as an adhesive hydrogel with polyvinylpyrrolidone K-25, polyethylene glycol 4000, and various permeation enhancers. The flux and permeability of ketoprofen were evaluated. As the concentration of tween 80 and enhancers increased, the flux of ketroprofen was accelerated. Also the permeation rate was facilitated by enhancers, but did not affect the lag time. From these results, the adhesive hydrogel using microsphere could be a good delivery system for ketoprofen to improve the skin permeation.

• Journal of Pharmaceutical Investigation
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• v.37 no.2
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• pp.73-78
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• 2007

The aim of this study was to investigate the absorption properties of ketoprofen. The in-situ perfusion model has advantages over in vitro models as it provides intact lymphatic and blood flow circulation. The absorption properties of six different concentrations of ketoprofen have been studied in single pass in-situ rat intestine model. $^{14}C-PEG$ 4000 was used as a permeability marker and the possibility of an energy dependent contribution to ketoprofen absorption was also Investigated using the metabolic inhibitor sodium azide. Three different concentrations of sodium azide were studied to examine its effect on absorption of ketoprofen from the rat intestine. The findings of this study suggest that mono-carboxylic type drugs like ketoprofen cause permeability changes in the intestine. This is shown by the increase in absorption of $^{14}C-PEG$ 4000 as the concentration of ketoprofen is increased. However, the trend for ketoprofen permeability is to decrease over the concentration ranges. It was observed that the Papp values for ketoprofen with sodium azide shows a trend towards reduction in the amount of ketoprofen absorbed from the rat intestine which was significantly different (p<0.05) from that of ketoprofen with sodium azide 3.0mM. This indicates that sodium azide has an affect on the absorption of ketoprofen. The pH of all the perfusion solutions was altered to ${\sim}pH\;6.7$ by the buffering capacity of the small intestine secretions. The results suggest that mechanisms other than passive diffusion may be involved in ketoprofen absorption. This would be consistent with the involvement of active transport or saturatable processes in the absorption of drugs containing monocarboxylic acid group, as has been previously suggested from in vitro data.

• Journal of Veterinary Clinics
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• v.23 no.4
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• pp.400-404
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• 2006

This study demonstrates the anti-arthritic effect of topical application of ketoprofen gel containing N-methyl-2-pyrrolidone (NMP) in adjuvant arthritis therapy. Adjuvant arthritis was induced by a single injection of Freund's complete adjuvant (FCA). Mature female Sprague-Dawley rats were designated to 3 groups such as control group, K10 group (ketoprofen 10 mg/rat), and NK10 group (ketoprofen 10 mg/rat containing NMP). The anti-arthritic activity of ketoprofen containing NMP was tested not only as to its capability to suppress the inflammatory edema, but also bone damage (X-ray score and regional bone uptake) of the hind paw in arthritis-induced rats. These results showed a higher efficacy of ketoprofen containing NMP than ketoprofen treatment in the adjuvant-induced arthritis. Ketoprofen containing NMP has good intrinsic characteristics for formulation in an efficacious anti-inflammatory topical application.

• Journal of the Korean Magnetic Resonance Society
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• v.15 no.1
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• pp.54-68
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• 2011

$^1H$ nuclear magnetic resonance (NMR) spectroscopy of biological samples has been proven to be an effective and nondestructive approach to probe drug toxicity within an organism. In this study, ketoprofen toxicity was investigated using $^1H$-NMR spectroscopy coupled with multivariate statistical analysis. Histopathologic test of ketoprofen-induced acute gastrointestinal damage in rats demonstrated a significant dose-dependent effect. Furthermore, principal component analysis (PCA) derived from $^1H$-NMR spectra of urinary samples showed clear separation between the vehicle-treated control and ketoprofen-treated groups. Moreover, PCA derived from endogenous metabolite concentrations through targeted profiling revealed a dose-dependent metabolic shift between the vehicle-treated control, low-dose ketoprofen-treated (10 mg/kg body weight), and high-dose ketoprofen-treated (50 mg/kg) groups coinciding with their gastric damage scores after ketoprofen administration. The resultant metabolic profiles demonstrated that the ketoprofen-induced gastric damage exhibited energy metabolism perturbations that increased urinary levels of citrate, cis-aconitate, succinate, and phosphocreatine. In addition, ketoprofen administration induced an enhancement of xenobiotic activity in fatty oxidation, which caused increase levels of N-isovalerylglycine, adipate, phenylacetylglycine, dimethylamine, betaine, hippurate, 3-indoxylsulfate, N,N-dimethylglycine, trimethyl-N-oxide, and glycine. These findings demonstrate that $^1H$-NMR-based urinary metabolic profiling can be used for noninvasive and rapid way to diagnose adverse drug effects and is suitable for explaining the possible biological pathways perturbed by nonsteroidal anti-inflammatory drug toxicity.

• The Korean Journal of Pain
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• v.11 no.2
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• pp.258-262
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• 1998

Background: In view of the safety and effectiveness of butorphanol as a postoperative analgesic, we designed to compare its activity and side effects with those of ketoprofen, when administered intramuscularly. Methods: Ninety four patients, scheduled for elective total abdominal hysterectomy, received either ketoprofen 100 mg (ketoprofen group) or butorphanol 2 mg (butorphanol group) intramuscularly after surgery. For the first six hours after injection of butorphanol or ketoprofen, the patients were asked to reevaluate the intensity of pain, using numeric rating scale (NRS) and pain score. If the pain score was above 2, supplemental ketoprofen was administered IM. Incidence of side effects were also checked. Results: Butorphanol group showed lower NRS and pain score for the first four hours compared to ketoprofen group, but the incidence of drowsiness was higher in butorphanol group. There were no significant difference in the incidence of other side effects such as nausea and dizziness. In both group, there were neither respiratory depression nor pruritus. Conclusions: Butorphanol gave better relief of postoperative pain compared to ketoprofen. Butorphanol might be a useful drug for postoperative analgesia after hysterectomy with minor side effects.

• Korean Chemical Engineering Research
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• v.47 no.1
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• pp.54-58
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• 2009

Ketoprofen and ibuprofen are non-steroid anti-inflammatory drug(NSAID) that have analgesic and antipyretic properties. (S)-ketoprofen and (S)-ibuprofen have pharmacological activity, while (R)-ketoprofen and (R)-ibuprofen are either inactive or have side effect. The chiral separation of racemic ketoprofen and ibuprofen enantiomers was carried out by using a Kromasil HPLC column. Some chromatographic parameters (selectivity, resolution, number of theoretical plates and ${\Delta}H$) are calculated under different mobile phase compositions of hexane/t-BME/acetic acid and temperatures. The selectivity, resolution and number of theoretical plates were observed high at $25^{\circ}C$ and the composition of hexane/t-BME/acetic acid (80/20/0.1).

• 한국생물공학회:학술대회논문집
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• 2001.11a
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• pp.693-696
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• 2001

Ketoprofen racemate is very useful pharmaceutical intermediate, but the hardness of separation to each enantiomer is most a barrier to apply pharmaceutical industry. To overcome this difficulty, we would like to separate S-ketoprofen from ketoprofen racemate. To design suitable mobile phase, hexane and t-BME(tri-buthyl-methyle-ether) were used to elute peaks of ketoprofen racemate separately. When the ratio of hexane/t-BME/acetic acid was 60/40/0.1(%v/v), each component was separated successfully. In order to separate large amount of S-ketoprofen, sample concentration was increased from 100ppm to 2000ppm. In this case, resolution was decreased due to the overlapping of peaks(1.65${\rightarrow}$0.94).