• YAKHAK HOEJI
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• v.52 no.3
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• pp.188-194
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• 2008

Fexofenadine, ($\pm$)-4-1-hydroxy-4-{4-(hydroxydiphenylmethyl)-1-piperidinyl}-butyl-a,a-dimethyl benzeneacetic acid, is a selective histamine $H_1$ receptor antagonist, and is clinically effective in the treatment of seasonal allergic rhinitis and chronic idiopathic urticaria as a first-line therapeutic agent. The purpose of the present study was to evaluate the bioequivalence of two fexofenadine hydrochloride tablets, $Allegra^{(R)}$ (Handok Pharmaceuticals Co., Ltd.) and Alecort (Samchundang Pharmaceutical Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of fexofenadine from the two fexofenadine hydrochloride formulations in vitro was tested using KP VIII Apparatus II method with various dissolution media. Twenty six healthy male subjects, 25.62$\pm$3.35 years in age and 70.05$\pm$11.71 kg in body weight, were divided into two groups and a randomized 2$\times$2 cross-over study was employed. After a single tablet containing 120 mg as fexofenadine hydrochloride was orally administered, blood samples were taken at predetermined time intervals and the concentrations of fexofenadine in serum were determined using HPLC with fluorescence detector. The dissolution profiles of two formulations were similar in all tested dissolution media. The harmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated, and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Allegra^{(R)}$, were -1.37, 5.22 and 16.50% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., log 0.83$\sim$log 1.08 and log 0.81$\sim$log 1.03 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Alecort tablet was bioequivalent to $Allegra^{(R)}$ tablet.

• Korean Journal of Breeding Science
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• v.49 no.3
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• pp.180-189
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• 2017

Genetically modified (GM) crops have been developed worldwide through the recombinant DNA technology and commercialized by global agricultural companies. Until now, GM crops have not been cultivated commercially in Korea. Commercialization of GM crops requires a compulsory assessment of environmental risk associated with the release of GM crops. This study was conducted to evaluate the frequency of pollen mediated gene flow from Bt transgenic rice (Agb0101) to japonica non-GM rice (Nakdongbyeo), indica non-GM rice (IR36), and weedy rice (R55). A total of 729,917, 596,318 and 230,635 seeds were collected from Nakdongbyeo, IR36, and R55, respectively, which were planted around Agb0101. Selection of the hybrids was determined by repeated spraying of herbicide and Cry1Ac1 immunostrip assay. Finally, the hybrids were confirmed by PCR analysis using specific primer. The hybrids were found in all non-GM rice and out-crossing ranged from 0.0005% at IR36 to 0.0027% at Nakdongbyeo. All of hybrids were located within 1.2 m distance from the Agb0101 rice plot. The meteorological elements including rainfall and temperature during rice flowering time were found to be important factors to determine rice out-crossing rate. Consideration should be taken for many factors like the meteorological elements of field and physiological condition of crop to set up the safety management guideline to prevention of GM crops gene flow.

• Journal of Pharmaceutical Investigation
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• v.35 no.3
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• pp.179-185
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• 2005

Acebrophylline is a compound produced by salifying ambroxol with theophylline-7 -acetic acid. After acebrophylline administration, the salt splits into these two components which feature a peculiar pharmacokinetic behavior, an adequate ambroxol and a low theophylline-7-acetic acid serum levels. The purpose of the present study was to evaluate the bioequivalence of two acebrophylline capsules, Surfolase (Hyundai Pharm. lnd. Co., Ltd.) and Burophil (Kuhnil Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of ambroxol from the two acebrophylline formulations in vitro was tested using KP VIII Apparatus II method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty eight healthy male subjects, $23.25{\pm}1.43$ years in age and $64.82{\pm}6.77$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After two capsules containing 100 mg as acebrophylline were orally administered, blood was taken at predetermined time intervals and the concentrations of ambroxol in serum were determined using HPLC with electrochemical detector (ECD). The dissolution profiles of two formulations were similar at all dissolution media. In addition, the pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug Surfolase, were -1.64, -3.33 and -0.92% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 $(e.g., \;log\;0.93{\sim}log\;1.05\;and\;log\;0.88{\sim}log\;1.05$ for $AUC_t$, and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Burophil capsule was bioequivalent to Surfolase capsule.

• Journal of Pharmaceutical Investigation
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• v.36 no.3
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• pp.209-215
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• 2006

Zaltoprofen, (2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid) is an NSAID with powerful anti-inflammatory effects as well as an analgesic action on inflammatory pain. The purpose of the present study was to evaluate the bioequivalence of two zaltoprofen tablets, $Soleton^{\circledR}$ (CJ Corp.) and SCD Zaltoprofen (Samchundang Pharmaceutical Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of zaltoprofen from the two zatoprofen formulations in vitro was tested using KP Vlll Apparatus ll method with various dissolution media. Twenty six healthy male subjects, $23.2{\pm}2.26$ years in age and$64.7{\pm}8.08$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single tablet containing 80 mg as zaltoprofen was orally administered, blood samples were taken at predetermined time intervals and the concentrations of zaltoprofen in serum were determined using HPLC with UV detector. The dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated, and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Soleton^{\circledR}$ were 6.33, 5.91 and 17.7% for $AUC_t$, $C_{max}$ and untransformed $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g.,log $1.01{\sim}1og\;1.11$ and log $0.928{\sim}1og\;1.18$ for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating SCD Zaltoprofen tablet was bioequivalent to $Soleton^{\circledR}$ tablet.

• Journal of the Society of Disaster Information
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• v.9 no.4
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• pp.449-461
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• 2013

As the hydrofluoric acid leak in Gumi-si, Gyeongsangbuk-do or hydrochloric acid leak in Ulsan, Gyeongsangnam-do demonstrated, chemical related accidents are mostly caused by large amounts of volatile toxic substances leaking due to the damages of storage tank or pipe lines of transporter. Safety assessment is the most important concern because such toxic material accidents cause human and material damages to the environment and atmosphere of the surrounding area. Therefore, in this study, a hydrofluoric acid leaked from a storage tank was selected as the study example to simulate the leaked substance diffusing into the atmosphere and result analysis was performed through the numerical Analysis and diffusion simulation of ALOHA(Areal Location of Hazardous Atmospheres). the results of a qualitative evaluation of HAZOP (Hazard Operability)was looked at to find that the flange leak, operation delay due to leakage of the valve and the hose, and toxic gas leak were danger factors. Possibility of fire from temperature, pressure and corrosion, nitrogen supply overpressure and toxic leak from internal corrosion of tank or pipe joints were also found to be high. ALOHA resulting effects were a little different depending on the input data of Dense Gas Model, however, the wind direction and speed, rather than atmospheric stability, played bigger role. Higher wind speed affected the diffusion of contaminant. In term of the diffusion concentration, both liquid and gas leaks resulted in almost the same $LC_{50}$ and ALOHA AEGL-3(Acute Exposure Guidline Level) values. Each scenarios showed almost identical results in ALOHA model. Therefore, a buffer distance of toxic gas can be determined by comparing the numerical analysis and the diffusion concentration to the IDLH(Immediately Dangerous to Life and Health). Such study will help perform the risk assessment of toxic leak more efficiently and be utilized in establishing community emergency response system properly.

• Journal of Soil and Groundwater Environment
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• v.12 no.1
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• pp.73-86
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• 2007

Risk-based remediation strategy (RBRS) is a consistent decision-making process for the assessment and response to chemical release based on protecting human health and the environment. The decision-making process described integrates exposure and risk assessment practices with site assessment activities and remedial action selection to ensure that the chosen actions are protective of human health and the environment. The general sequences of events in Tier 1 is as follows: initial site assessment, development of conceptual site model with all exposure pathways, data collection on pollutants and receptors, and identification of risk-based screening level (RBSL). If site conditions do not meet RBSL, it needs further site-specific tier evaluation, Tier 2. In most cases, only limited number of exposure pathways, exposure scenarios, and chemicals of concern are considered the Tier 2 evaluation since many are eliminated from consideration during the Tier 1 evaluation. In spite of uncertainties due to the conservatism applied to risk calculations, limitation in site-specific data collections, and variables affecting the selection of target risk levels and exposure factors, RBRS provides us time- and cost-effectiveness of the remedial action. To ensure reliance of the results, the development team should consider land and resource use, cumulative risks, and additive effects. In addition, it is necessary to develop appropriate site assessment guideline and reliable toxicity assessment method, and to study on site-specific parameters and exposure parameters in Korea.

• Journal of Pharmaceutical Investigation
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• v.31 no.4
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• pp.289-295
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• 2001

Carvedilol is an antihypertensive and antianginal compound that combines nonselective beta-adrenoceptor blocking and vasodilation properties and is devoid of intrinsic sympathomimetic activity. The purpose of the present study was to evaluate the bioequivalence of two carvedilol tablets, $Dilatrend^{TM}$ (Chong Kun Dang Pharmaceutical Co., Ltd.) and $Carvelol^{TM}$ (Dae Won Pharmaceutical Co., Ltd.), according to the prior and revised guidelines of Korea Food and Drug Administration (KFDA). The carvedilol release from the two carvedilol tablets in vitro was tested using KP VII Apparatus II method with various different kinds of dissolution media (pH 1.2, 4.0, 6.8 buffer solution, water and blend of PSB80 into water). Eighteen normal male volunteers, $24.22{\pm}1.86$ years in age and $64.81{\pm}4.56\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 25 mg of carvedilol was orally administered, blood was taken at predetermined time intervals and the concentrations of carvedilol in serum were determined using HPLC method with fluorescence detector. The dissolution profiles of two carvedilol tablets were very similar at all dissolution media. Besides, the pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using non-transformed and logarithmically transformed $AUC_t$ and $C_{max}$. The results showed that the differences in $AUC_t$, $C_{max}$ and $T_{max}$ between two tablets based on the $Dilatrend^{TM}$ were 2.23%, -2.00% and 0.00%, respectively. Minimum detectable differences $({\Delta})$ at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 13.55% and 17.61% for $AUC_t$ and $C_{max}$, respectively). The powers $(l-{\beta})$ at ${\alpha}=0.05$, ${\Delta}=0.2$ for $AUC_t$ and $C_{max}$ were 98.08% and 88.81%, respectively. The 90% confidence intervals were within ${\pm}20%$ (e.g., $-5.69{\sim}10.16$ and $-12.30{\sim}8.30$ for $AUC_t$ and $C_{max}$, respectively). There were no sequence effect between two tablets in logarithmically transformed $AUC_t$ and $C_{max}$. The 90% confidence intervals using logarithmically transformed were within the acceptance range of log(0.8) to log(1.25) (e.g., $0.95{\sim}1.11$ and $0.89{\sim}1.09$ for $AUC_t$ and $C_{max}$, respectively). Two parameters met the criteria of prior and revised KFDA guideline for bioequivalence, indicating that $Carvelol^{TM}$ tablet is bioequivalent to $Dilatrend^{TM}$ tablet.

• Korean Journal of Ecology and Environment
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• v.41 no.2
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• pp.216-227
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• 2008

To understand eutrophication in the upper regions of brackish Lake Sihwa with a limited water exchange, temporal and spatial distributions of pollutants in water and sediment were investigated from March to October in 2005 and 2006. Also, pollution levels of water and sediment were estimated by trophic state index (TSI) and sediment quality guideline (SQG). Total nitrogen (TN), total phosphorus (TP), organic matter (COD), and chlorophyll $\alpha$ (Chl-$\alpha$) concentrations in the surface waters were largely varied temporally and spatially, and the variations were highest in the middle areas where strong halocline was formed. Chl-$\alpha$ concentrations in the middle area were very high in April (>$900\;{\mu}g\;L^{-1}$) when algal blooms (red tides) occurred. The relationships between TN and Chl-$\alpha$ (r=0.31), and TP and Chl-$\alpha$ (r=0.65) indicated that the algal growth was primarily affected by phosphorus rather than nitrogen. The distribution of COD was similar to that of Chl-$\alpha$, indicating that the autochthonous organic matters may be a more important carbon source, especially in the middle areas. The brackish water regions were classified as eutrophic or hypertrophic based on their TSI values ($69{\sim}76$). In addition, the content of nutrients (especially TP) in surface sediments were classified as severe polluted state, except the upper areas. Major causes of the eutrophication observed were probably due to high nutrients loading from watersheds, the phosphorus release from anaerobic sediment, and long retention time by the limited water exchange through the sluice gates.

• Tuberculosis and Respiratory Diseases
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• v.53 no.3
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• pp.294-308
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• 2002

Background : The cell-mediated immune response plays an important role in tuberculosis. After being activated by mycobacterial antigens, T lymphocytes express a high affinity receptor (IL-2R) for interleukin-2 (IL-2) on their own surface and release a soluble fraction of the IL-2 receptor (sIL-2R) from the cell membrane into the circulation. Neopterin is a metabolite of guanosine-triphosphate, which is produced by stimulated macrophages under the influence of IFN-$\gamma$ with a T lymphocyte origin. Therefore, the utility of sIL-2R, IFN-$\gamma$ and the neopterin levels as immunologic indices of the cell-mediated immune response and severity of disease in patients with pulmonary tuberculosis was assessed. Methods : The serum sIL-2R, IFN-$\gamma$ and neopterin levels were measured in 39 patients with pulmonary tuberculosis, 6 patients with tuberculous lymphadenitis prior to treatment and 10 healthy subjects. The serum and pleural sIL-2R, neopterin and ADA levels were measured in 22 patients with tuberculous pleurisy. The patients with pulmonary tuberculosis were divided into a mild, moderate and severe group according to the severity by ATS guidelines. To compare the results from these patients with those of the pretreatment levels, the sIL-2R, IFN-$\gamma$ and neopterin levels were measured in 36 of the 39 patients(1 patient, expired; 2 patients were referred to a sanitarium) with pulmonary tuberculosis after 2 months of treatment. Results : 1) the serum sIL-2R and IFN-$\gamma$ levels were elevated in patients with tuberculosis when compared to those of healthy subjects (p>0.05). The neopterin concentration in the serum was significantly lower in patients with pulmonary tuberculosis($2967{\pm}2132.8$ pg/ml) than in healthy controls($4949{\pm}1242.1$ pg/ml)(p<0.05). 2) In the pulmonary tuberculosis group, the serum sIL-2R and IFN-$\gamma$ levels were higher in patients with severe disease than those in patients with mild and moderate disease. However, the neopterin levels declined as the pulmonary tuberculosis became more severe (p<0.01). 3) The mean serum sIL-2R and IFN-$\gamma$ levels declined from $1071{\pm}1139.4$ U/ml to $1023{\pm}1920.9$ U/ml(p>0.05), $41{\pm}52.8$ pg/ml to $22{\pm}23.9$ gm/ml(p<0.05), respectively, after 2 month of treatment. The mean serum neopterin levels increased from $3158{\pm}2272.6$ pg/ml to $3737{\pm}2307.5$ pg/ml(p>0.05) after a 2 month of treatment. These findings were remarkable in the severe group of pulmonary tuberculosis with a clinical correlation. 4) In the patients with tuberculous pleurisy, the serum sIL-2R and ADA were significantly higher than those in the pleural fluid, However, the neopterin levels in the sera and pleural effusion were similar. Conclusion : On the basis of this study, sIL-2R, IFN-$\gamma$ and neopterin measurements may not only provide an insight into the present state of the cell-mediated immune response, but also serve as parameters monitoring of the prognosis of the disease, particularly in patients with severe pulmonary tuberculosis. In addition, an assay of the pleural sIL-2R levels might signal a stimulated local immunity including T cell activation in the tuberculous pleural effusion.