• Journal of Pharmaceutical Investigation
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• v.35 no.5
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• pp.323-328
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• 2005

The purpose of the present study was to evaluate the bioequivalence of two torasemide tablets, Torem tablet (Roche Korea Co., Ltd., Korea, reference drug) and Boryung Torsemide tablet (Boryung Pharmaceutical Co., Ltd., Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). After adding an internal standard (furosemide) to human serum, serum samples were extracted using 5 mL of ethyl acetate. Compounds were analyzed by reverse-phase HPLC method with UV detection. This method showed linear response over the concentration range of 0.05 ug/mL with correlation coefficient of 0.999. The lower limit of quantitation using 0.5 mL of serum was 0.05 ug/mL which was sensitive enough for pharmacokinetic studies. Twenty-eight healthy male Korean volunteers received each medicine at the torasemide dose of 20 mg in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Serum concentrations of torasemide were monitored by an HPLC-UV for over a period of 12 hr after the administration. $AUC_{t}$(the area under the serum concentration-time curve from time zero to 12 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum serum drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the serum concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_{t}$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_{t}$ ratio and the $C_{max}$ ratio for Boryung Torsemide/Torem were log 0.97-10g 1.03 and log 0.93log 1.12, respectively. These values were within the acceptable bioequivalence intervals of log 0.80-log 1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating Boryung Torsemide tablet and Torem tablet are bioequivalent.

• Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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• v.15 no.4
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• pp.381-390
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• 2017

In Korea, commercial nuclear power plants and research reactors have on-site storage systems for the spent nuclear fuel, but it is difficult to expand the facilities used for the storage systems. If decommissioning of nuclear power plants starts, an amount of high level radioactive waste will be generated. In this study, a radiological impact assessment of the railroad transport of high level radioactive waste was carried out considering radiation workers and the public, using the developed transport container as the transport package. The dose rates for workers and the public during the transport period were estimated, considering anticipated transport scenarios, and the results compared with the regulatory limit. A sensitivity analysis was also carried out by considering the different release ratios of the radioactive materials in the high level radioactive waste, and different distances between the transport container and workers during loading and unloading phases and while attaching another freight car. For all the anticipated transport scenarios, the radiological impacts for workers and the public met the regulatory limits.

• Journal of Environmental Health Sciences
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• v.31 no.6
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• pp.457-466
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• 2005

Industrial plasticizers such as phthalates can induce peroxisome proliferation. A growing concern among environmental and health groups has arisen because phthalates such as di-2-ethy1hexy1 phthalate (DEHP) and DBP may cause hormonal disorders, reproductive toxicity, hepatocellular tumors, genital disorders owing to a capacity to bind estrogen receptors, and a low-dose toxic action during certain periods of fetal development. Phthalate esters are used extensively as a plasticizer for plastic manufacture such as PVC bags and medical devices. This study investigated the effects of leached components from spring water container's cap and seal film. Phthalates, e.g. dimethy1 phthalate (DMP), diethy1 phthalate (DEP), di-n-buty1 phthalate (DBP), benzy1buty1 phthalate (BBP), di-(2-ethy1hexy1) phthalate (DEHP), and bisphenol A (BPA) were measured in the spring water. The bisphenol A was not detected or below the detection limit on the leaching from cap, sealing or spring water. DEHP were detected 90-116 ppb on the leaching from seal after 2 weeks, and 0.48-0.51 ppb from the spring water after I week. BBP were measured from seal within 1 week 25.4-66 ppb and below 0.12 ppb from spring water within 2 days. DMP were detected from seal within 2 weeks 51-68.5 ppb and 0.12 ppb after 2 weeks. DEP were measured from seal within 2 weeks 48.1-141 ppb and the concentrations were increased by the time from 0.10 to 0.31 ppb at spring water. DBP were detected from the seal within 2 weeks 92.3-5100 ppb and the concentration were decreased by the time from 0.24 to 0.10 ppb at spring water. These results indicate that some phthalate esters contaminated with spring water using the intact cap and seal film. It is concluded that the measured levels of phthalates leaching from these materials might in vivo only be slightly less than 1/10 of the LOAEL.

• Biomolecules & Therapeutics
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• v.19 no.1
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• pp.38-44
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• 2011

Cisplatin is widely used for various types of cancers. However, its side effects, most notably, renal toxicity often limit its clinical utility. Although previous metabolomic studies reported possible toxicity markers, they used small number of animals and statistical approaches that may not perform best in the presence of intra-group variation. Here, we identified urinary biomarkers associated with renal toxicity induced by cisplatin using NMR-based metabolomics combined with Orthogonal Projections to Latent Structures-Discriminant Analysis (OPLS-DA). Male Sprague-Dawley rats (n=22) were treated with cisplatin (10 mg/kg single dose), and the urines obtained before and after treatment were analyzed by NMR. Multivariable analysis of NMR data presented clear separation between non-treated and treated groups. The OPLS-DA statistical results revealed that 1,3-dimethylurate, taurine, glucose, glycine and branched-chain amino acid (isoleucine, leucine and valine) were significantly elevated in the treated group and that phenylacetylglycine and sarcosine levels were decreased in the treated group. To test the robustness of the approach, we built a prediction model for the toxicity and were able to predict all the unknown samples (n=14) correctly. We believe the proposed NMR-based metabolomics with OPLS-DA approach and the resulting urine markers can be used to augment the currently available blood markers.

• Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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• v.20 no.1
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• pp.63-67
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• 2009

Background and Objectives: In patients with asthma, increased obstruction and resistance of airway result in impairment in the generation of voice. Allergy and nasal polyposis, which are frequently observed in patients with asthma, are other factors that affect the vocal performance. Bronchodilators and steroids are commonly used in the treatment of asthma, and these agents also have been reported to be associated with voice changes. The aim of this study is to evaluate the voice quality in patients with mild to-moderate asthma by subjective and objective methods. Materials and Methods: A total of 36 patients with asthma established in the Department of Respiratory Medicine were included in this study. 23 were women and 13 were men, with a mean age of 51.7 years. The average duration of asthma was 77.0 months. All patients had mild-to moderate asthma. Acoustic and aerodynamic analyses were performed and the movements of the vocal cords were examined by videolaryngostroboscopy (VLS). Voice Handicap Index (VHI) and GRABS scales were used for subjective evaluations. Results: 50% of patients suffered from dysphonia and FO was 119.3${\pm}$23.7 Hz in male and 198.2${\pm}$18.4 Hz in female patients. There were no significant differences in average shimmer and NHR between females (4.90${\pm}$2.95% ; 0.1O${\pm}$0.04 dB) and males (4.64${\pm}$2.45% ; 0.20${\pm}$0.15 dB). However, the value of jitter was greater for females (2.60${\pm}$1.92%) than for males (1.21${\pm}$0.84%). The VHI score was above the normal limit in 35%, and VLS findings were shown diverse abnormality in 89% asthmatics from mucosal change to hyperfunction of supragottis and contact granuloma. But duration of illness and steroid dose did not correlate with these findings. Conclusion: Subjective and objective abnormality was shown in more than 50% of asthmatic patients. We suggest that persons who suffer from asthma should be examined for possible voice disorders by laryngologist. Additionally, appropriate medical care and voice therapy should be provided for those who have voice disorders associated with asthma.

• Fire Science and Engineering
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• v.21 no.3
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• pp.15-23
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• 2007

In the events of a fire in the residential building, highly flammable polyurethane foam sofa produce toxic smokes. In this type of fire, the residents of the building can be gotten into the difficulties of evacuating from the fire places or may be to death due to a lot of hot toxic gases. In this study, CFD simulations were carried out to study the effects of the openings of stairwell on the fire characteristics of fire room and stairwell. Also, analysis of fire hazard based on the tenability limits of fire and FED(fractional effective dose) was performed to evaluate the life safety of the residents of the building. In the fire room, maximum temperature was about $290^{\circ}C$, maximum CO concentration was about 4,740 ppm, and the time to incapacitation of residents in fire room was about t=144 s. In the stairwell, temperature and CO concentration in the condition of openings to be open were even lower than those in it to be closed. Time to the tenability limit with respect to smoke visibility in the stairwell with openings, which was open, was shorter than that of it without openings to be open. It has been shown from this study that opening the stairwell openings is able to decrease the fire hazards to the life safety in the multi-story residential building fire.

• Biomolecules & Therapeutics
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• v.9 no.4
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• pp.291-297
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• 2001

The bioequivalence of two triflusal products was evaluated with 20 healthy volunteers following single oral dose according to the guidelines of Korea Food and Drug Administration (KFDA). Trisa $l^{R}$ capsule (Whanin Pharm. Corp., Korea) and Disgre $n^{R}$ capsule (Myung-In Pharm. Corp., Korea) were used as test product and reference product, respectively. Both products contain 300 mg of trifusal. One capsule of test product or reference product was orally administered to the volunteers, respectively, by randomized two period crossover study (2$\times$2 Latin square method). Blood samples were taken at predetermined time intervals for 4 hours and the determination of trifusal was accomplished using semi-microbore HPLC equipped with automated column switching system. The analytical method with HPLC was validated according to the Bioanalytic Method Validation guideline by F7A prior to determining the plasma samples. The pharmacokinetic parameters (AU $C_{0-4h}$ $C_{max}$ and $T_{max}$) were calculated and ANOVA test was utilized for statistical analysis of parameters. As a result of the assay validation, the limit of quantification of trifusal in human plasma by current assay procedure was 50 ng/ml using 500 $\mu$l of plasma. The accuracy of the assay was from 97.76% to 116.51% while the intra-day and inter-day coefficient of variation of the same concentration range was less than 15%. Average drug concentration at the designated time intervals and pharmacokinetic parameters calculated were not significantly different between two products (p>0.05). The difference of mean AU $C_{olongrightarrow4hr}$, $C_{max}$, and $T_{max}$ between the two products (2.92, 4.39, and -2.44%, respectively) were less than 20%. The power (1-$\beta$) and treatment difference ($\Delta$) for AU $C_{olongrightarrow4hr}$ and $C_{max}$ were more than 0.8 and less than 0.2, respectively. Although the power for $T_{max}$ was under 0.8, $T_{max}$ of the two products was not significantly different from each other (p>0.05). These results satisfied the criteria of KFDA guideline for bioequivalence, indicating the two products of triflusal were bioequivalent.quivalent.ent.ent.

• Journal of Pharmaceutical Investigation
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• v.37 no.5
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• pp.315-321
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• 2007

The purpose of the present study was to evaluate the bioequivalence of two lercanidipine hydrochloride tablets, Zanidip tablet (LG Life Sciences Ltd., Korea, reference drug) and Samchundang Lercanidipine tablet 10 mg (Sam Chun Dang Pharm. Co. Ltd., Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). After adding an internal standard (amlodipine maleate) to human serum, serum samples were extracted using hexan-isoamyl alcohol (100:1, v/v). Compounds were analyzed by liquid chromatography/tandem mass spectrometry. This method showed linear response over the concentration range of 0.05-20 ng/mL with correlation coefficient of 0.9999. The lower limit of quantitation using 0.5 mL of serum was 0.05 ng/mL which was sensitive enough for pharmacokinetic studies. Thirty healthy male Korean volunteers received each medicine at the lercanidipine hydrochloride dose of 20 mg in a $2\;{\times}\;2$ crossover study. There was a one-week washout period between the doses. Serum concentrations of lercanidipine were monitored by an LC/MS/MS fer over a period of 24 hr after the administration. $AUC_t$ (the area under the serum concentration-time curve from time 0 to 24 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (the maximum serum drug concentration) and $T_{max}$ (the time to reach $C_{max}$) were compiled from the serum concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters, indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for Samchundang Lercanidipine/Zanidip were log 0.9505-log 1.2258 and log 0.9987-log 1.2013, respectively. These values were within the acceptable bioequivalence intervals of log 0.80-log 1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating Samchundang Lercanidipine tablet 10 mg and Zanidip tablet are bioequivalent.

• Journal of Pharmaceutical Investigation
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• v.40 no.2
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• pp.109-115
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• 2010

The purpose of the present study was to evaluate the bioequivalence of two choline alphoscerate soft capsules, Gliatilin soft capsule (Daewoong Pharmaceuticals Co., Ltd.) and Cholicerin soft capsule (Sam Chun Dang Pharm. Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Serum concentrations of choline after oral administration of choline alphoscerate were determined using a validated LC/MS/MS method. This method showed linear response over the concentration range of 0.5-20 ${\mu}g$/mL with correlation coefficient of 0.9999. The lower limit of quantitation using 100 ${\mu}L$ of serum was 0.5 ${\mu}g$/mL which was sensitive enough for pharmacokinetic studies. Thirty six healthy male Korean volunteers received each medicine at the choline alphoscerate dose of 1200 mg in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Blood samples were taken at predetermined time intervals up to 8 hr. $AUC_t$ (the area under the serum concentration-time curve from time 0 to 8 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (the maximum serum drug concentration) and $T_{max}$ (the time to reach $C_{max}$) were compiled from the serum concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters, indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for Cholicerin/Gliatilin were log0.9998-log1.1172 and log0.9938-1.0944, respectively. These values were within the acceptable bioequivalence intervals of log0.80-log1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating Cholicerin soft capsule and Gliatilin soft capsule are bioequivalent.

• Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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• v.12 no.2
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• pp.121-133
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• 2014

If the spent fuels or the high-level radioactive wastes can be disposed of in the depth of 3~5 km and more stable rock formation, it has several advantages. For example, (1)significant fluid flow through basement rock is prevented, in part, by low permeability, poorly connected transport pathways, and (2)overburden self-sealing. (3)Deep fluids also resist vertical movement because they are density stratified and reducing conditions will sharply limit solubility of most dose-critical radionuclides at the depth. Finally, (4) high ionic strengths of deep fluids will prevent colloidal transport. Therefore, as an alternative disposal concept to the deep geological disposal concept(DGD), very deep borehole disposal(DBD) technology is under consideration in number of countries in terms of its outstanding safety and cost effectiveness. In this paper, for the preliminary applicability analyses of the DBD system for the spent fuels or high level wastes, the DBD concepts which have been developed by some countries according to the rapid advance in the development of drilling technology were reviewed. To do this, the general concept of DBD system was checked and the study cases of foreign countries were described and analyzed. These results will be used as an input for the analyses of applicability for DBD in Korea.