• Journal of Pharmaceutical Investigation
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• 제12권2호
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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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• 제13권2호
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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 $1.02{\times}10^4\;M^{-1}$.

• 한국임상수의학회지
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• 제16권1호
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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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• 제25권3호
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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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• 제37권2호
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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.

• 한국임상수의학회지
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• 제23권4권
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• pp.400-404
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• 2006

본 연구는 랫드의 우측 후지 발바닥에 Freund's complete adjuvant를 투여하여 관절염을 유발한 후에 N-methyl-2-pyrrolidone (NMP) 기제를 첨가한 경피용 ketoprofen 제제의 관절염 치료 효과를 확인하기 위해서 수행되었다. NMP를 함유한 ketoprofen 경피용 제제의 관절염 치료 효과를 알아보기 위해서 Sprague-Dawley 암칫 랫드를 대조군과 약물 투여군으로 분리하고, 약물 투여군은 ketoprofen 10mg/rat 투여군(K10군)과 NMP가 함유된 ketoprofen 10mg/rat 투여군(NK10군)으로 분류하였다. 실험적 관절염을 유발시킨 후 $^{99m}Tc-MDP$을 이용한 bone scan에서 골병변이 나타난 7일 후부터 14일 동안 약물을 매일 한번씩 랫드의 등에 극소 도포하여 다음과 같은 결론을 얻었다. NMP의 기제를 첨가한 ketoprofen 경피용 제제가 ketoprofen단독 경피용 제제 보다 후지 부종을 현저하게 감소시켰고 단순 방사선 사진과 scintigraphy에서 관절염에 의한 골 파괴를 효과적으로 억제하였다. 이상의 연구 결과를 기초로 하여 관절염 치료에 있어 NMP를 함유한 ketoprofen 경피용 제제가 ketoprofen단독 제제보다 효과가 있다는 결론을 얻을 수 있었다.

• 한국자기공명학회논문지
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• 제15권1호
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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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• 제11권2호
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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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• 제47권1호
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• pp.54-58
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• 2009

Ketoprofen과 Ibuprofen은 비스테로이드 계통의 진통 및 소염제로서 관절염 등을 위한 진통제나 해열제로 이미 널리 사용되고 있다. 그러나 이 두 물질이 치료약으로 사용될 때 (S)-ketoprofen과 (S)-ibuprofen은 약리학적으로 항염증 작용을 하며 (R)-ketoprofen과 (R)-ibuprofen은 약효가 없거나 부작용을 일으키는 문제점을 가지고 있다. 본 연구에서는 Ketoprofen과 Ibuprofen을 Kromasil HPLC 칼럼을 사용하여 이동상 조성비(hexane/t-BME/acetic acid)와 온도 변화($25{\sim}55^{\circ}C$)가 분리에 미치는 영향을 실험하였다. 분리특성은 선택도, 분리도, 이론단수 그리고 용량인자와 절대온도의 역수사이의 관계에서 계산된 엔탈피 변화 ${\Delta}H$에서 Ketoprofen과 Ibuprofen의 kromasil HPLC column 고정상과의 상호작용의 크기를 열역학적으로 검토하였다. 온도 $25^{\circ}C$, 이동상 조성비(hexane/t-BME/acetic acid) 80/20/0.1에서 선택도, 분리도, 이론단수 엔탈피 수치가 높게 나타났다.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2001년도 추계학술발표대회
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• pp.693-696
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• 2001

Ketoprofen racemate를 각 enantiomer로 분리하고자 이동상의 조성을 변화하여 실험을 수행한 결과, hexane과 t-BME의 비가 60/40(%v/v)인 경우 적합한 체류시간과 분리도를 얻을 수 있었으며, 이동상의 acetic aicd를 0.1%(v/v) 첨가한 경우 낮은 pH에서 분리가 효율적으로 일어났다. 또한, 시료의 농도를 변화시켜 실험을 수행한 경우, 2000ppm까지는 선택도에 큰 변화없이 분리를 수행할 수 있었으나, 농도가 1000ppm 이상인 경우 분리도가 1.00미만으로 낮은 값을 보였다.