• YAKHAK HOEJI
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• v.47 no.5
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• pp.261-265
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• 2003

Near-infrared (NIR) system was used to determine rapidly and simply indomethacin in buffer solution for a dissolution test of tablets and capsules. Indomethacin standards were prepared ranging from 10 to 50 ppm using the mixture of phosphate buffer (pH 7.2) and water (1 : 4). The near-infrared (NIR) transmittance spectra of indomethacin standard solutions were collected by using a quartz cell in 1 mm and 2 mm pathlength. Partial least square regression (PLSR) was explored to develop calibration models over the spectral range 1100∼1700 nm. The model using 1 mm quartz cell was better than that using 2 mm quartz cell. The PLSR models developed gave standard error of prediction (SEP) of 0.858 ppm. In order to validate the developed calibration model, routine analysis was performed using another standard solutions. The NIR routine analysis showed good correlation with actual values. Standard error of prediction (SEP) is 1.414 ppm for 7 indomethacin samples in routine analysis and its error was permeable in the regulation of Korean Pharmacopoeia (VII). These results show the potential use of the real time monitoring for indomethacin during a dissolution test.

• Korean Journal of Veterinary Research
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• v.25 no.1
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• pp.27-32
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• 1985

배란 및 착상시기에 indomethacin 투여가 혈액의 progesterone 수준과 착상율에 미치는 영향을 조사하였다. Progesterone수준은 HCG 주사후 4시간이내에 9ng/ml로 증가 되었다가 배란시에는 3ng/ml로 감소하였다. indomethacin투여구에서는 배란시 8ng/ml를 나타내기 까지 계속증가하였다. Indomethacin투여는 착상을 억제하였다. 대조구의 착상율은 83%이나, indomethacin을 HCG 주사후 1일부터 4일까지 투여하면 착상율은 63%, HCG주사후 5일 부터 8일까지 투여하면 착상율은 27%로 감소하였다. Progesterone 수준은 HCG 주사후 12ng/ml의 높은 수준을 나타내다가 HCG 주사후 3일까지는 3ng/ml이하의 낮은 수준을 나타내였으며 4일 부터는 10ng/ml의 높은 수준을 나타냈다. Indomethacin을 HCG 주사후 5일부터 8일까지 투여하면 HCG 주사후 3일까지는 대조구와 비슷하지만 4일 부터는 5ng/ml이하로 대조구 보다 낮은 수준을 나타냈다.

• Clinical and Experimental Pediatrics
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• v.51 no.9
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• pp.956-963
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• 2008

Purpose : Indomethacin is widely used for the prophylaxis and treatment of patent ductus arteriosus (PDA); however, it is associated with side effects such as renal failure, intraventricular hemorrhage, and gastrointestinal bleeding. Intravenous ibuprofen has been shown to be as effective as indomethacin in prompting PDA closure. If treatment with oral ibuprofen is as effective as indomethacin, it would have the advantages of greater availability, simpler administration, and lower cost. We conducted this study to compare the efficacy and side effects of indomethacin with those of oral ibuprofen, vis-$\grave{a}$-vis on the pharmacological closure of PDA. Methods : As a randomized double-blind study, 34 preterm infants with respiratory distress syndrome and hemodynamically significant PDA were treated with either intravenous indomethacin or oral ibuprofen. Echocardiography was performed by one cardiologist who was blind to the treatment that any given infant received. The rate of ductal closure, the need for additional drug treatment or surgical ligation, clinical outcome, and the side effects of drug treatment were compared. Results : Ductal closure occurred in 16 of 18 patients (88.9%) from the indomethacin group and in 14 of 16 patients (87.5%) from the ibuprofen group (P>0.05). Three patients in the indomethacin group and four in the ibuprofen group required a second drug treatment (P>0.05). Three patients (i.e., one patient in the indomethacin group and two in the ibuprofen group) underwent surgical ligation (P>0.05). Between the two groups, there was no significant difference vis-$\grave{a}$-vis in side effects or clinical outcome. Conclusion : Compared to indomethacin, oral ibuprofen has the advantages of simpler administration and lower cost, while being as effective; in addition, there are no differences between the two drug treatments with regards to side effects or clinical outcomes. Therefore, the widespread use of oral ibuprofen should be considered in treating PDA in preterm infants.

• YAKHAK HOEJI
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• v.20 no.1
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• pp.76-82
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• 1976

The base-catalyzed hydrolysis of indomethacin over a range of pH 8,2 to 10.0 was investigated, according to the first order kinetic equation. The energy of activation for the reaction was calculated 20, 18 kcal/mole from the Arrhenius plot. And the optimal pH of indomethacin in aqueous solution was estimated as pH 4.93 by the extrapolation of the log k-pH profiles in strong acidic and alkaline regions. And the influences of alkaline earth metals, heavy metals and some other compounds on the degradation of indomethacin were observed with no effect.

• Journal of Microbiology and Biotechnology
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• v.21 no.4
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• pp.400-404
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• 2011

Indomethacin is a nonsteroid anti-inflammatory agent that is known to induce severe gastric mucosal lesions. In this study, we investigated the effect of selenium on gastric mucosal lesions in rats. To confirm the curative effect of selenium against indomethacin-induced gastric ulcers, gastric ulcers were induced by oral administration of 25 mg/kg indomethacin, and then different doses (10, 50, and 100 ${\mu}g$/kg of body weight) of selenium or vehicle were treated by oral gavage for 3 days. Oral administration of indomethacin clearly increased the gastric ulcer area in the stomach, whereas selenium applied for 3 days significantly decreased the gastric ulcer area in a dose-dependent manner. In addition, selenium markedly reduced the increase of lipid peroxidation induced by indomethacin in the gastric mucosa and increased activities of radical scavenging enzymes such as superoxide dismutase, catalase, and glutathione peroxidase in a dose-dependent manner. These results reveal that selenium can heal indomethacin-induced gastric ulcers through elimination of the lipid peroxides and activation of radical scavenging enzymes.

• The Journal of Korean Medicine
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• v.36 no.4
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• pp.42-55
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• 2015

Purpose: The object of this study is to observe the anti-ulcerative effects of BK-1202 (IGM), a mixed herbal formula consisting of 9 herbal drugs, which have been traditional Korean medicine for treating various digestive diseases, on indomethacin-induced gastric ulcer in rat. Methods: Three different doses of IGM extract (200, 100 and 50 mg/kg) were orally administered once 30 min before indomethacin treatment. Six hours after indomethacin treatment, changes in the gross lesion scores, fundic histopathology, MPO activity and antioxidant activities were observed. The results were compared with two reference groups treated with omeprazole (10 mg/kg), antioxidant and proton pump inhibitor, and DA-9601 (100 mg/kg), a standardized extract of the herb Artemisiaasiatica. Results: In all three doses of IGM extract, significantly decreased gastric damages were observed in the indomethacin-induced gastric ulcer rats, when compared with the indomethacin-treated control rats. IGM extracts also strengthened the antioxidative defense systems, decreasing the level of lipid peroxidation and catalase activity while increasing the superoxide dismutase and glutathione contents. IGM extracts showed similar anti-ulcerative effects to those shown by equal dose of DA-9601, and the effects of 50 mg/kg IGM extracts were comparable to those of 10 mg/kg omeprazole. Conclusion: The results obtained in this study suggest that IGM extract has favorable effects on the indomethacin -induced gastric damages by strengthening the antioxidative defense systems and enhancing anti-inflammatory effects.

• YAKHAK HOEJI
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• v.45 no.6
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• pp.715-723
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• 2001

Indomethacin is well known as a prostaglandin (PG) E$_2$ synthetase inhibitor which has antipyretic and anti-inflammatory effects and reduces the risk of cancer Growing tumors greatly induce hypersensitive responses to lipopolysaccharide (LPS). Thus, this study was investigated the effect of indomethacin on the LPS-induced production of cytokines in sarcoma-bearing ICR mice. Indomethacin at doses of 5mg/kg was administered orally 30 minutes before i.p. injection of LPS (8 mg/kg) 5 times for 7 days. LPS remarkedly increased tumor necrosis factor (TNF)-$\alpha$ and interleukin (IL)-1$\beta$, levels in both serum and splenic supernatants compared with those in controls, while indomethacin significantly reduced the LPS-increased levels of IL-1$\beta$, in both serum and supernatants. LPS significantly enhanced IL-2 levels in serum and interferon (IFN)-${\gamma}$ levels in supernatants, whereas indomethacin did not affect the LPS-increased levels of IL-2 and IFN-${\gamma}$. These data, therefore, indicate that indomethacin may attenuate the pathogenesis of IL-1$\beta$, induced by LPS and maintain the tumoricidal cellular immune effects by LPS-increased production of IL- 2 and IFN-${\gamma}$ in tumor-bearing state.

• The Journal of Korean Medicine
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• v.19 no.1
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• pp.165-178
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• 1998

This study was carried out to investigate the protective effects of GaMiHyangSaYukGunJaTang on gastric mucosal lesions caused by indomethacin in rats.The test group was injected with indomethacin after the oral administration of GaMiHyangSaYukGunJaTang, while the control group was injected only with indomethacin. The lipid peroxidation level increased considerably in the control group, but superoxide disnurtase(SOD), catalase and glutathione(GSH) levels remarkably decreased. The following effects induced by indomethacin were observed in the stomach of the control group; mucosa hemoIThagic infarct, mucosa cell necrosis, leukocyte appearance, mucosa hemorrhagic erosion and gastric pit disawearance. In the test group, lipid peroxides level was significantly reduced compared with the control group While SOD, catalase and GSH levels considerably increased. The following effects were also observed in the stomach of the test group; mucosa hemorrhagic infarct, mucosa cell necrosis, leukocyte appearance and mucosa hemorrhagic erosion occured far less and gastric pit disappearance was not observed at all. This results suggest that GaMiHyangSaYukGunJaTang is effective in the remedy of gastric mucosal lesions as GaMiHyangSaYukGunJaTang suppresses the production of the lipid peroxides and free radicals induced by indomethacin and activates SOD, catalase and GSH.

• The Journal of Korean Medicine
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• v.28 no.2 s.70
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• pp.166-184
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• 2007

Objectives : This study was conducted to investigate the effects of Daegeum-eumja, Igwi-tang, and Sihosogan-san on gastric mucosal lesions induced by alcohol, indomethacin, and burn-stress in mice. Methods : Experimental mice were divided into six groups. The normal group (NOR) did not receive any treatment to elicit gastropathy. In the control group (GE), gastropathy was elicited by alcohol, indomethacin, and stress. In the misoprostol group (MS), misoprostol was administered after gastropathy was elicited by alcohol, indomethacin, and stress. In the Daegeum-eumja group (DG), Daegeum-eumja was administered after gastropathy was elicited by alcohol, indomethacin, and stress. In the Igwi-tang group (IW), Igwi-tang was administered after gastropathy was elicited by alcohol, indomethacin, and stress. In the Sihosogan-san group (SH), Sihosogan-san was administered after gastropathy waselicited by alcohol, indomethacin, and stress. The effects on gastric mucosal lesions were evaluated by the morphological change of gastric mucosa, the anti-oxidant effect, HSP 70, $NF-{\kappa}B$ p65, $I{\kappa}B$, COX-1, PNA, BrdU, and iNOS. Results : Hemorrhage erosion, HSP70, and $NF-{\kappa}B$ in the DG, IW and SH groups decreased more than that of the control. The $I{\kappa}B$, COX-1, PNA, BrdU, and iNOS in the DG, IW, and SH groups increased more than that of the control. DG showed the most effect against gastric mucosal lesions induced by alcohol; IW against gastric mucosal lesions induced by indomethacin; and SH against gastric mucosal lesions induced by burn-stress. Conclusions: Daegeum-eumja, Igwi-tang, and Sihosogan-san extracts have excellent effects on gastric mucosal lesions induced by alcohol, indomethacin, and burn-stress, respectively.

• YAKHAK HOEJI
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• v.46 no.4
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• pp.258-264
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• 2002

Zinc plays an important role in immunobiological responses, while excessive zinc attenuates immune functions in a dose-dependent manner. Zinc excess has been reported to increase levels of plasma prostaglandin E$_2$ (PGE$_2$), which is known to inhibit production of Th (helper T) 1-associated cytokines and to induce inflammatory responses. Thus, this study was investigated the effects of indomethacin, a potent inhibitor of PGE$_2$ synthesis, on the proinflammatory cytokine and lymphokine production in ICR mice exposed to excessive zinc. Indomethacin at doses of 5 mg/kg was administered i.p. 30 minutes before zinc chloride (Zn) 30 mg/kg orally daily for 10 days. Excessive Zn remarkedly increased tumor necrosis factor (TNF)-$\alpha$ and interleukin (IL)-1$\beta$ levels in both serum and splenic supernatants compared with those in controls, while indomethacin significantly reduced the excessive Zn-induced levels of IL-1$\beta$. In serum, excessive Zn significantly decreased the levels of IL-2 and interferon (IFN)-${\gamma}$ compared with those in controls, whereas indomethacin significantly enhanced the excessive Zn-decreased levels of IFN-${\gamma}$ but did not affect the Zn-decreased levels of serum IL-2. In splenic supernatants, All of excessive Zn, indomethacin, and combination of Zn and indomethacin significantly enhanced IL-2 levels compared with those in controls, but indomethacin didn't affect the Zn-induced production of IL-2. These data, therefore, suggest that indomethacin significantly attenuated the in vivo and ex vivo IL-1$\beta$ production increased by excessive zinc and remarkedly enhanced the in vivo excessive zinc-suppressed production of IFN-${\gamma}$ but not IL-2.