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Bioequivalence of Alpit Tablet to Algiron Tablet (Cimetropium Bromide 50 mg) (알기론 정(브롬화 시메트로피움 50 mg)에 대한 알피트 정의 생물학적 동등성)

  • Cho, Hea-Young;Moon, Jai-Dong;Lee, Yong-Bok
    • Journal of Pharmaceutical Investigation
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    • v.32 no.1
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    • pp.47-54
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    • 2002
  • Cimetropium bromide, a quaternary ammonium compound which is chemically related to scopolamine, exhibits its antispasmodic activity by competing with acetylcholine for the muscarinic receptors of the smooth muscle of gastrointestinal tract. The drug has been used for the treatment of various disorders involving spasms of the musculature of the gastrointestinal, biliary and genitourinary tracts. The purpose of the present study was to evaluate the bioequivalence of two cimetropium bromide tablets, $Algiron^{TM}$ (Boehringer Ingelheim Korea Ltd.) and $Alpit^{TM}$ (Hana Pharmaceutical Co., Ltd.), according to the prior and revised guidelines of Korea Food and Drug Administration (KFDA). The cimetropium bromide release from the two cimetropium bromide 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 and water). Twenty normal male volunteers, $25.25{\pm}2.10$ years in age and $65.76{\pm}6.39$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After three tablets containing 50 mg of cimetropium bromide per tablet were orally administered, blood was taken at predetermined time intervals and the concentrations of cimetropium bromide in serum were determined using HPLC method with UV detector. The dissolution profiles of two cimetropium bromide 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 $Algiron^{TM}$ were 2.19%, -5.97% and 3.49%, respectively. Minimum detectable differences $({\Delta})\;at \;{\alpha}=0.05\;and\;1-{\beta}=0.8$ were less than 20% (e.g., 13.71 %, 19.05% and 15.11% for $AUC_t,\;C_{max}\;and\;T_{max}$, respectively). The powers $(1-{\beta})\;at\;{\alpha}=0.05,\;{\Delta}=0.2\;for\;AUC_t$, $C_{max}\;and\;T_{max}$ were 97.79%, 83.22% and 95.60%, respectively. The 90% confidence intervals were within ${\pm}20%$ (e.g., $-5.84{\sim}10.21,\;-17.11{\sim}5.18\;and\;-5.35{\sim}12.33\;for\;AUC_t,\;C_{max}\;and\;T_{max}$, respectively). There were no sequence effect between two tablets in logarithmically transformed $AUC_t\;and\;C_{max}$. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) (e.g., $0.94{\sim}1.10\;and\;0.85{\sim}1.05\;for\;AUC_t\;and\;C_{max}$, respectively). Two parameters met the criteria of prior and revised KFDA guideline for bioequivalence, indicating that $Alpit^{TM}$ tablet is bioequivalent to $Algiron^{TM}$ tablet.

Bioequivalence of Rispen Tablet to Risperdal Tablet (Risperidone 2 mg) (리스페달 정(리스페리돈 2mg)에 대한 리스펜 정의 생물학적 동등성)

  • Cho, Hea-Young;Park, Eun-Ja;Kang, Hyun-Ah;Baek, Seung-Hee;Lee, Suk;Park, Chan-Ho;Moon, Jai-Dong;Lee, Yong-Bok
    • Journal of Pharmaceutical Investigation
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    • v.34 no.2
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    • pp.139-145
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    • 2004
  • The purpose of the present study was to evaluate the bioequivalence of two risperidone tablets, Risperdal (Janssen Korea Co., Ltd.) and Rispen (Myung In Pharm. Co., Ltd), according to the guidelines of Korea Food and Drug Administration (KFDA). The risperidone release from the two risperidone formulations in vitro was tested using KP VIII Apparatus II method with various of dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty four healthy male subjects, $23.33\;{\pm}2.10$ years in age and $69.24{\pm}8.05\;kg$ kg in body weight, were divided into two groups and a randomized $2\;{\times}\;2$ cross over study was employed. After one tablet containing 2 mg as risperidone was orally administered, blood was taken at predetermined time intervals and the concentrations of risperidone in serum were determined using HPLC method with UV detector. The dissolution profiles of two formulations were 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 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 Risperdal were 0.20, -1.29 and -11-09% for $AUC_t$,$C_{max},\;and\;T_{max}$, respectively There were no sequence effects two formulations in parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) (e.g.,$log(0.90){\sim}log(1.30)$ and $log(0.84){\sim}log(1.09)$ for$AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA guideline for the bioequivalence were satisfied, indicating Rispen tablet and Risperdal tablet were bioequivalent.

Bioequivalence of Glimed Tablet to Amaryl Tablet (Glimepiride 2 mg) (아마릴 정(글리메피리드 2mg)에 대한 글리메드 정의 생물학적 동등성)

  • Cho, Hea-Young;Park, Eun-Ja;Kang, Hyun-Ah;Baek, Seung-Hee;Lee, Suk;Kim, Se-Mi;Moon, Jai-Dong;Lee, Yong-Bok
    • Journal of Pharmaceutical Investigation
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    • v.34 no.2
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    • pp.147-153
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    • 2004
  • The purpose of the present study was to evaluate the bioequivalence of two glimepiride tablets, $Amaryl^{\circledR}$ (Handok/Aventis Pharm. Co., Ltd.) and Glimed (Kuhn II Pharm. Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The glimepiride release from the two glimepiride formulations in vitro was tested using KP VIII Apparatus II method with a variety of dissolution media (pH 1.2, 4.0, 6.8 buffer solution, water and blend of PSB 80 into each dissolution medium). Twenty six healthy male subjects, $22.65{\pm}2.19$ years in age and $66.55{\pm}8.85$ kg in body weight, were divided into two groups and a randomized $2\;{\times}\;2$ cross-over study was employed. After one tablet containing 2 mg as glimepiride was orally administered, blood was taken at predetermined time intervals and the concentrations of glimepiride in serum were determined using HPLC method with UV detector. The dissolution profiles of two formulations were 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 logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the Amaryl were -3.70, -8.28 and 0.61% 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., $log(0.84){\sim}log(1.04)$ for $log(0.82){\sim}log(1.03)$ for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA guideline for the bioequivalence were satisfied, indicating Glimed tablet and Amaryl tablet were bioequivalent.

Bioequivalence of Tagamet Tablet to Sinil CIMETIDINE Tablet (cimetidine 400 mg) (타가메트정 400 mg에 대한 신일시메티딘정 400 mg의 생물학적동등성시험)

  • Yoon, Mi-Kyeong;Lee, Byoung-Moo;Lee, Sung-Jae;Kim, Sun-Kyu;Lee, Jae-Hwi;Choi, Young-Wook
    • Journal of Pharmaceutical Investigation
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    • v.34 no.6
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    • pp.521-527
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    • 2004
  • Cimetidine is a histamine $H_2-receptor$ antagonist, used for the treatment of endoscopically or radiographically comfirmed duodenal ulcer, pathologic GI hypersecretory conditions, and active, benign and gastric ulcer. Simple method for determining cimetidine in human plasma has been developed and validated. The analytical procedure for cimetidine showed a linear relationship in the concentration ranges from $0.05\;to\;5\;{\mu}g/ml$. Coefficient of variance (CV, %) for intraday and interday validation and relative error (RE, %) were less than ${\pm}15%$. Based on this analytical method, the bioequivalence of two cimetidine 400 mg tablets, reference (Tagamet 400 mg) and test drug (Sinil CIMETIDINE 400 mg) was evaluated according to the guidelines set by the Korea Food and Drug Administration (KFDA). Release of cimetidine from the tablets in vitro was tested using KP VIII Apparatus II with various dissolution media (pH 1.2, 4.0, 6.8 buffer solutions and water). Twenty-four healthy volunteers, $21.38{\pm}1.86$ years in age and $68.71{\pm}8.68\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was performed. After oral administration of a tablet containing 400 mg of cimetidine, blood samples were taken at predetermined time intervals and concentrations of cimetidine in plasma were determined using HPLC equipped with UV detector. The dissolution profiles of the two tablet formulations were very similar at all dissolution media. In addition, pharmacokinetic parameters such as $AUC_t$ and $C_{max}$ were calculated and ANOVA was employed for the statistical analysis of parameters. The results were revealed that the differences in $AUC_t$ and $C_{max}$ between the two tablets were 4.17 % and 0.97% respectively. At 90% confidence intervals, the differences in these parameters were also within ${\pm}20%$. All of the above mentioned parameters have met the criteria of KFDA guidelines for bioequivalence, indicating that the test drug tablet (Sinil CIMETIDINE tablet) is bioequivalent to Tagamet 400 mg tablet.

Pull-out Resistance Characteristics of the Anchor Bar According to the Grouting Material (주입재료에 따른 Anchor Bar의 인발저항 특성)

  • Yea, Geu-Guwen;Song, Young-Suk
    • The Journal of Engineering Geology
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    • v.18 no.2
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    • pp.227-232
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    • 2008
  • In this study, the pull out resistance characteristics of an anchor bar to support a spillway installed in a slope are investigated by field tests. The injection materials were a cement mortar and cement milk. Unconfined compression strengths of those materials under several conditions were measured. As the result of compression test, the unconfined compression strengths of the cement mortar and the cement milk have positive proportional relation-ship with the water-cement ratio. They also have negative proportional relationship with increasing the curing time. In the same condition of water-cement ratio and curing time, the unconfined compression strength of cement milk is larger than that of cement mortar. In order to reduce the eccentricity in anchor bar during pull-out test in the field, the installation apparatus was improved by inserting a nut type of steel fixing coupling into the anchor bar. As the result of the pull-out test, the strength modification of cement milk was increased steeply at the early curing time. However, that of cement mortar was increased gradually with passing the curing time. Therefore, the cement milk has to use as the injection material for a prompt construction of anchor bar because the strength modification of cement milk is occurred at the early curing time.

The Effect of Substrates and Nitrate on Biological Phosphorus Release (생물학적 인 방출시 유기물 및 질산염에 대한 영향)

  • Min, Kyung-Kook;Weon, Seung-Yeon;Lee, Sang-Ill
    • Journal of Korean Society of Environmental Engineers
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    • v.22 no.1
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    • pp.141-148
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    • 2000
  • In this study, effects of substrates and nitrate on biological phosphorus release in EBPR(enhanced biological phosphorus removal) process were examined using batch test apparatus at anaerobic conditions. The sludge used in this experiments was taken from SBR(sequencing batch reactor) treating swine wastewater at aeration period. Phosphorus release rates obtained with substrates of FSW(fermented swine wastewater), acetate, propionate, domestic wastewater and methanol were 6.19, 5.99, 1.52, 1.2 and $1.03mgP/gVSS{\cdot}hr$, respectively. Those observed with acetate and FSW were 4~5 times greater than those with propionate, methanol and domestic wastewater. Therefore phosphorus release rates were significantly affected by type of substrate added at anaerobic condition. Phosphorus release was greatly affected by concentration of nitrate in anoxic condition. Comparing to acetate, propionate and FSW, phosphorus release was observed after almost completely depletion of nitrate concentration with methanol and domestic wastewater added as substrate. In the cases supplied with acetate, propionate and FSW, phosphorus release rates were less influenced by a nitrate concentration than those with methanol and domestic wastewater.

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추적자를 이용한 오염물질 거동분석

  • Kim, Gi-Cheol;Lee, Jong-Seok;Lee, Jae-Cheol;Kim, Yun-Ho;Yeon, Gi-Heum
    • Proceedings of the Korea Contents Association Conference
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    • 2008.05a
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    • pp.289-293
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    • 2008
  • In this study, in order to find out the movement of polluted substance that is flown into the river and the characteristics of dispersion, the experiment that used the RI (Radio Isotope) tracer in the river was undertaken, and by using the experiment result, the figure modelling was undertaken to analyze the general type of pollutant dispersion. In addition, in order to calculate more accurate dispersion range and moving time, the experiment was done in about 2km from the measuring points of Namdaecheon around the Yongdam Dam of the upper Geum River to the lower stream, and modeling was undertaken for the 20km zone from the measuring points to the lower stream. In order to find out the flow of river and dispersion of polluted substance, RMA (Resource Modeling Associates)-2 and RMA-4 program are used in study. The site experiment using the RI was implemented for the experiment in the applied area and the same area, and the distance between each zone was set for 1㎞ with the slight difference for site situation and measured the density date of one second distance through the NaI apparatus to measure the density data of one second interval. On the basis of this measured data, it is compared and analyzed with the result of figure copy of RMA-2 and RMA-4 models to make the comparison and analysis of density distribution following the change in expansion coefficient that makes great influence on expansion range and dispersion in natural rivers. The influence of expansion coefficient on river can be researched and the measured density data, the maximum and minimum density time, and the basic data to calculate the expansion coefficient was prepared in this study.

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Freshness Prolongation of Crisphead Lettuce by Vacuum Cooling (진공예냉처리에 의한 양상치의 선도 연장)

  • Kim, Dong-Chul;Lee, Se-Eun;Nahmgoong, Bae;Choi, Mun-Jeong;Jeong, Mun-Cheol;Kim, Byeong-Sam
    • Applied Biological Chemistry
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    • v.38 no.3
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    • pp.239-247
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    • 1995
  • The improvement of distribution system and freshness prolongation of crisphead lettuce were carried out through vacuum cooling and distribution under the low temperature. Lettuce that vacuum-cooled and transported by cold storage car was shown better freshness than that distributed by conventional method when they arrived at cunsuming area. And it took $10{\sim}17$ hours until their temperatures arrived at same temperatures when they were stored at $0{\sim}15^{\circ}C$ cold storage room. It was cooled to $1^{\circ}C$ after 27 minutes with vacuum cooling apparatus. The weight loss of lettuce that vacuum cooled and transported by cold storage car was below 5% after 30 days cold storage. And ascorbic acid and chlorophyll retentions were 86% and 52%, respectively. The shelf-life of crisphead lettuce, distributed by vacuum cooling and cold storage car transportation, was 5 days at $15^{\circ}C$ and over 40 days at $0^{\circ}C$, respectively. However, when it was distributed by conventional method, it was only 3 days at $15^{\circ}C$ and 20 days at $0^{\circ}C$, respectively.

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The Effect of Delayed Compaction on Unconfined Compressive Strength of Soil-Cement Mixtures (지연다짐이 Soil-Cement의 압축강도에 미치는 영향)

  • 정일웅;김문기;도덕현
    • Magazine of the Korean Society of Agricultural Engineers
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    • v.28 no.4
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    • pp.66-76
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    • 1986
  • This study was attempted to investigate the effects of delayed compaction on the unconfined compressive strengh and dry density of Soil-cement mixtures. Soil-cement construction is a time-consuming procedure. Time-delay is known as a detrimental factor to lower the quality of soil-cement layer. A laboratory test was performed using coarse and fine weathered granite soils. The soils were mixed with 7% cement at optimum moisture content and excess moisture content in part. Socondary additives such as lime, gypsum-plaster, flyash and sugar were tried to counteract the detri-mental effect of delayed compaction. The specimens were compacted by Harvard Miniature Compaction Apparatus at 0,1,2,4,6 hors after mixing. Two kinds of compactive efforts(9 kgf and 18 kgf tamper) were applied. The results were summarized as follows: 1.With the increase of time delay, the decrease rate of dry density of the specimen compacted by 9 kgf tamper was steeper than that of the specimen compacted by 18kgf tamper. In the same manner, soil-B had steeper decreasing rate of dry density than soil-A. 2.Based on the results of delayed compaction tests, the dry density and unconfined compressive sterngth were rapidly decreased in the early 2 hours delay, while those were slowly decreased during the time delay of 2 to 6 hours. 3.The dry density and unconfined compressive strength were increased by addition of 3% excess water to the optimum moisture content during the time delay of 2 to 6 hours. 4.Without time delay in compaction, the dry densities of soil-A were increased by adding secondary additives such as lime, gypsum-plaster, flyash and sugar, on the other hand, those of soil-B were decreased except for the case of sugar. 5.The use of secondary additives like lime, gypsum-plaster, flyash and sugar could reduce the decrease of unconfined compressive strength due to delayed compaction. Among them, lime was the most effective. 6.From the above mentioned results, several recommendations could be suggested in order to compensate for losses of unconfined compressive strenght and densit v due to delayed compaction. They are a) to use coarse-grained granite soil rather than fined-grained one, b) to add about 3% excess compaction moisture content, c) to increase compactive effort to a certain degree, and d) to use secondary additives like line gypsum-plaster, flyash, and sugar in proper quantity depending on the soil types.

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Effect of Calcium Chloride (CaCl2) on the Characteristics of Photosynthetic Apparatus, Stomatal Conductance, and Fluorescence Image of the Leaves of Cornus kousa (염화칼슘 처리가 산딸나무 잎의 광합성 기구, 기공전도도 및 형광이미지 특성에 미치는 영향)

  • Sung, Joo-Han;Je, Sun-Mi;Kim, Sun-Hee;Kim, Young-Kul
    • Korean Journal of Agricultural and Forest Meteorology
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    • v.11 no.4
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    • pp.143-150
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    • 2009
  • Deicing salt is used to melt snow and ice on the road for traffic safety during the winter season, which accumulates in the roadside vegetation and induces visible injuries. The damage may accelerate particularly when it coincides with early spring leaf out. In order to better understand the response mechanisms, C. kousa (3-year-old) was irrigated twice prior to leaf bud in a rhizosphere with solutions of 0.5, 1.0, and 3.0% calcium chloride ($CaCl_2$) concentration, that were made by using an industrial $CaCl_2$ reagent practical deicing material in Seoul. Physiological traits of the mature leaves were progressively reduced by $CaCl_2$ treatment, resulting in reductions of total chlorophyll contents, chlorophyll a:b, photosynthetic rate, quantum yield, stomatal conductance, $F_V/F_M$, and NPQ. On the contrary, light compensation point and dark respiration were increased at high $CaCl_2$ concentration. A decrease in intercellular $CO_2$ concentration by stomatal closure first resulted in a reduced photosynthetic rate and then was accompanied by low substance metabolic rates and photochemical damage. Based on the reduction of physiological activities at all treatments ($CaCl_2$ 0.5%, 1.0%, and 3.0%), C. kousa was determined as one of the sensitive species to $CaCl_2$.