Evaluation of the Efficacy and Safety of DA-9601 versus Its New Formulation, DA-5204, in Patients with Gastritis: Phase III, Randomized, Double-Blind, Non-Inferiority Study

Choi, Yoon Jin,Lee, Dong Ho,Choi, Myung-Gyu,Lee, Sung Joon,Kim, Sung Kook,Song, Geun Am,Rhee, Poong-Lyul,Jung, Hwoon-Yong,Kang, Dae-Hwan,Lee, Yong Chan,Lee, Si Hyung,Choi, Suck Chei,Shim, Ki-Nam,Seol, KOREAN ACADEMY OF MEDICAL SCIENCE 2017 JOURNAL OF KOREAN MEDICAL SCIENCE Vol.32 No.11

<P>This study compared the efficacy of DA-9601 (Dong-A ST Co., Seoul, Korea) and its new formulation, DA-5204 (Dong-A ST Co.), for treating erosive gastritis. This phase III, randomized, multicenter, double-blind, non-inferiority trial randomly assigned 434 patients with endoscopically proven gastric mucosal erosions into two groups: DA-9601 3 times daily or DA-5,204 twice daily for 2 weeks. The final analysis included 421 patients (DA-5204, 209; DA-9601, 212). The primary endpoint (rate of effective gastric erosion healing) and secondary endpoints (cure rate of endoscopic erosion and gastrointestinal [GI] symptom relief) were assessed using endoscopy after the treatment. Drug-related adverse events (AEs), including GI symptoms, were also compared. At week 2, gastric healing rates with DA-5204 and DA-9601 were 42.1% (88/209) and 42.5% (90/212), respectively. The difference between the groups was −0.4% (95% confidence interval, −9.8% to 9.1%), which was above the non-inferiority margin of −14%. The cure rate of gastric erosion in both groups was 37.3%. The improvement rates of GI symptoms with DA-5204 and DA-9601 were 40.4% and 40.8%, respectively. There were no statistically significant differences between the two groups in both secondary endpoints. AEs were reported in 18 (8.4%) patients in the DA-5204 group and 19 (8.8%) in the DA-9601 group. Rates of AE were not different between the two groups. No serious AE or adverse drug reaction (ADR) occurred. These results demonstrate the non-inferiority of DA-5204 compared to DA-9601. DA-5204 is as effective as DA-9601 in the treatment of erosive gastritis. Registered randomized clinical trial at ClinicalTrials.gov (NCT02282670)</P>

조혈모세포이식 환자에서 침습성 진균 감염에 대한 이트라코나졸 액과 플루코나졸 시럽의 예방 효과 : 전향적, 무작위, 비교 임상시험

최수미,이동건,최정현,박선희,엄기성,김유진,김희제,민창기,유진홍,김동욱,이종욱,민우성,신완식,김춘추 대한감염학회 2005 감염과 화학요법 Vol.37 No.2

목적 : 조혈모세포이식 환자에서 호중구 감소 기간 동안 이트라코나졸 액(ITZS)과 플루코나졸 시럽(FCZS)의 진균 감염에 대한 예방 효과를 전향적으로 비교해 보고자 하였다. 재료 및 방법 : 2001년 8월부터 2002년 6월까지 가톨릭 조혈모세포이식센터에 입원하여 동종 조혈모세포이식을 받은 만 18세 이상의 환자들을 각각 ITZS와 FCZS군으로 무작위 배정하여 침습성 진균 감염 발생과 약제 관련 부작용을 전향적으로 조사하였다. 결과 : ITZS군에 40명, FCZS군에 38명이 배정되었고, FCZS군 환자의 평균 나이가 더 많았다. 시험 약제 평균투여기간은 ITZS군 16.4일, FCZS군 21.9일로 ITZS군이 더 짧았다. 이는 ITZS군에서 소화기 부작용으로 인한 약제 중단이 더 많았기 때문으로 보인다. 시험 약제 투여 후 총 빌리루빈 수치의 유의한 증가가 관찰되었으나, 약제 관련 부작용은 모든 환자에서 가역적이었다. 호중구감소 기간동안 표재성 진균 감염은 두 군에서 모두 발생하지 않았고, 침습성 진균 감염은 ITZS군 5명(12.5%), FCZS군 8명(21.1%)으로 FCZS군에서 많았으나, 통계학적으로 유의하지 않았고, 사망률에도 유의한 차이는 없었다. 결론 : 침습성 진균 감염에 대한 이트라코나졸 액과플루코라졸 시럽의 예방 효과에 유의한 차이는 없었으나, 앞으로 더 많은 환자를 대상으로 잘 짝지어진 대조군 연구가 필요할 것으로 보인다. 부작용 중 간독성과 관련하여 이식시 투여되는 여러 약제들과의 상호작용에 대한 연구도 필요할 것이다. Background : Though fluconazole is widely used for antifungal prophylaxis, it is ineffective against mould infections including Aspergillus species. Itraconazole has a broader spectrum than fluconazole but the capsule form shows erratic bioavailability in neutropenic patients. In this study, we compared itraconazole oral solution (ITZS) with fluconazole syrup (FCZS) for the prevention of invasive fungal infection (IFI) in allogeneic hematopoietic stem cell transplant recipients. Materials and Methods : Adults receiving allogeneic hematopoietic stem cell transplantation (HSCT) from september 2001 to June 2002, were randomly allocated to either the ITZS group or the FCZS group. We prospectively evaluated the safety and efficacy of each drug. Results : Out of 78 patients (40 patients in the ITZS group and 38 patients in the FCZS group) who were eligible for this study, 37 patients completed the course of prophylaxis without any evidence of IFI. The mean duration of prophylaxis was 16.4 days for the ITZS group and 21.9 days for the FCZS group (P<0.006). Drug-related adverse events occurred in 28 patients (70.0%) and 19 patients (50.0%) in the ITZS group and the FCZS group, respectively. Common adverse events of ITZS were nausea, vomiting, and diarrhea. Drug-related reversible hepatotoxicity occurred in 4 patients in the ITZS group. There was a significant elevation of total bilirubin level in the ITZS group. The incidence of suspected IFI occurred in 5 patients (12.5%) who received ITZS, compared with 8 (21.1%) who received FCZS (P=0.372). There were no proven IFIs or superficial (oral/vaginal) fungal infections in both groups. Overall mortality was not different between the two groups (2.5% in the ITZS group versus 5.3% in the FCZS group, P=0.610). Conclusion : ITZS and FCZS showed similar protection against IFI during pre-engraftment period. Poor tolerability due to gastrointestinal troubles of ITZS might limit its success as prophylactic therapy. Well matched controlled study with large number of patients will be required in the future.

조혈모세포이식 환자에서 발생한 Cytomegalovirus 질환의 특징 : 일개 대학변원에서 최근 10년간의 경험

최수미,이동건,박선희,김시현,김유진,민창기,김희제,이석,최정현,유진홍,김동욱,이종욱,민우성,신완식,김춘추 대한감염학회 2009 감염과 화학요법 Vol.41 No.1

Background : Studies on cytomegalovirus (CMV) diseases in Korean hematopoietic stem cell transplant (HSCT) recipients are lacking and do not reflect the recent trends of advances and changes. Therefore, we tried to analyze the clinical features of CMV diseases in HSCT recipients over the past 10 years at a tertiary university hospital in Korea. Methods : Retrospective review of medical records was done for all adult HSCT patients who received transplant at the Catholic HSCT Center from January 1998 to January 2008. Results : Forty-four cases (2.2%) of CMV diseases were identified. CMV pneumonia was diagnosed in 17 patients, retinitis in 16 patients, enterocolitis in 7 patients, esophagitis 1 patient, gastritis in 1 patient, duodenitis in 1 patient, and hepatitis in 1 patient. The median onset of symptom was 90 days after transplantation. Late CMV diseases accounted for 47.7%. CMV related death varied from 0 to 58.8% according to the involved organ. CMV retinitis was diagnosed relatively later in the course of transplantation mostly in patients who had chronic graft versus host disease (GVHD). On the contrary, CMV enterocolitis mainly occurred in patients who suffered from acute GVHD. The overall concurrent CMV reactivation was documented to be 63.6%: the concurrent CMV reactivation was observed only in 37.5% of patients with retinitis. Conclusions : We observed some differences in the pattern of CMV disease manifestation according to the involved organ and reconfirmed the fact that CMV pneumonia is the most common and fatal disease in HSCT recipients. Additionally, CMV retinitis was not uncommon in HSCT recipients. Since specific marker does not exist in predicting retinitis, regular ocular examination should be done thoroughly, especially in patients with chronic GVHD.

Bioequivalence Evaluation of Two Brands of Cefixime 100 mg Capsule (Suprax and Alpha-Cefixime) in Korean Healthy Volunteers

( Dong Hyun Choi ),( Jin Pil Burm ) 한국응용약물학회 2007 Biomolecules & Therapeutics(구 응용약물학회지) Vol.15 No.3

Cefixime is an orally absorbed cephalosporin with a broad spectrum of activity against Gram-negative bacteria and is highly resistant to beta-lactamase degradation. The purpose of the present study was to evaluate the bioequivalence of two cefixime capsules, Suprax capsule (Dong-A Pharmaceutical Co., reference drug) and Alpha-Cefixime capsule (Alpha Pharmaceutical Co., test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four normal subjects, 23.5±3.72 years in age and 68.3±8.89 kg in body weight, were divided into two groups and a randomized 2×2 cross-over study was employed. There was one week washout period between the doses. After one capsule containing 100 mg of cefixime was orally administered, plasma was taken at predetermined time intervals and the concentrations of cefixime in plasma were determined using HPLC with UV detector. 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. The results showed that the differences in AUC(t), C(max) and T(max) between two products were -3.91%, -2.23% and -3.18%, respectively, when calculated against the reference drug. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log0.8≤δ≤log1.25 (e.g., log0.8786≤δ≤log1.0523 and log0.8889≤δ≤log1.0512 for AUC(t) and C(max), respectively). The 90% confidence intervals using untransformed data was within ±20% (e.g., -10.37%≤δ≤6.73% for T(max)). All parameters met the criteria of KFDA for bioequivalence, indicating that Alpha-Cefixime capsule (Alpha Pharmaceutical Co.) is bioequivalent to Suprax capsule (Dong-A Pharmaceutical Co.).

Bioequivalence Evaluation of Two Brands of Cefixime 100 mg Capsule (Suprax and Alpha-Cefixime) in Korean Healthy Volunteers

Choi, Dong-Hyun,Burm, Jin-Pil The Korean Society of Applied Pharmacology 2007 Biomolecules & Therapeutics(구 응용약물학회지) Vol. No.

Cefixime is an orally absorbed cephalosporin with a broad spectrum of activity against Gram-negative bacteria and is highly resistant to beta-lactamase degradation. The purpose of the present study was to evaluate the bioequivalence of two cefixime capsules, Suprax capsule (Dong-A Pharmaceutical Co., reference drug) and Alpha-Cefixime capsule (Alpha Pharmaceutical Co., test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four normal subjects, $23.5{\pm}3.72$ years in age and $68.3{\pm}8.89$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. There was one week washout period between the doses. After one capsule containing 100 mg of cefixime was orally administered, plasma was taken at predetermined time intervals and the concentrations of cefixime in plasma were determined using HPLC with UV detector. 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. The results showed that the differences in $AUC_{t}$, $C_{max}$ and $T_{max}$ between two products were -3.91%, -2.23% and -3.18%, respectively, when calculated against the reference drug. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of $log0.8{\leq}{\delta}{\leq}log1.25$ (e.g., $log0.8786{\leq}{\delta}{\leq}log1.0523$ and $log0.8889{\leq}{\delta}{\leq}log1.0512$ for $AUC_{t}$ and $C_{max}$, respectively). The 90% confidence intervals using untransformed data was within ${\pm}20%$(e.g., $-10.37%{\leq}{\delta}{\leq}6.73%$ for $T_{max}$). All parameters met the criteria of KFDA for bioequivalence, indicating that Alpha-Cefixime capsule (Alpha Pharmaceutical Co.) is bioequivalent to Suprax capsule (Dong-A Pharmaceutical Co.).

Induction of Apoptosis by Cordycepin via Reactive Oxygen Species Generation in Human Leukemia Cells

Jin-Woo Jeong,Cheng-Yun Jin,Gi Young Kim,Cheol Park,Yung Hyun Choi,Jae Dong Lee 한국버섯학회 2009 한국버섯학회지 Vol.7 No.4

Cordycepin (3’-deoxyadenosin), a polyadenylation specific inhibitor, is the main functional component in Cordyceps militaris which is one of the top three famous traditional Chinese medicine. It has been shown to possess many pharmacological activities including immunologically stimulating, anti-cancer, anti-bacterial, and anti-virus, anti-infection effects. However, its anti-cancer molecular mechanisms are poorly understood. In this study, the apoptotic effects by cordycepin were investigates in human leukemia cells. Treatment of cordycepin significantly inhibited cells growth in a concentrationdependent manner by inducing apoptosis, as evidenced by morphological change and apoptotic cell death such as formation of apoptotic bodies, DNA fragmentation and increased populations of sub-G1. Induction of apoptosis by cordycepin was associated with modulation of Bcl-2 and inhibitor of apoptosis proteins (IAP) family expression. Cordycepin also increased reactive oxygen species (ROS) generation, activation of casepase-3, caspase-8, caspase-9, cleavage of poly(ADP-ribose) polymerase (PARP), β-catenin and phospholipase C (PLC)-γ1 protein. The quenching of ROS generation by N-acetyl-L-cysteine administration, a scavenger of ROS, reversed the cordycepin-induced apoptosis effects. Theresults suggested that cordycepin may be a potential chemotherapeutic agent for the treatment of leukemia patients [This work was supported by Blue-Bio Industry RIC at Dong-Eui University as a RIC (08-06-07) program of ITEP under Ministry of Knowledge Economy].

주택연금 수익비 분석에 관한 연구

최경진(Choi, Kyung-Jin),이동화(Lee, Dong-Hwa) 한국경영교육학회 2020 경영교육연구 Vol.35 No.4

[연구목적] 주택연금은 생존 시 자신의 소유주택에 거주하면서 월지급금을 받을 수 있을 뿐 만 아니라 사망 시 주택처분가액이 대출잔액에 비해 높을 경우 그 차액에 대해 상속이 가능하다. 그러나 이러한 장점에도 불구하고 월지급금에 대한 불만족으로 주택연금의 가입률은 저조한 상황이다. 본 연구에서는 주택연금의 장점을 반영한 연령 및 주택가격별 가입자의 수익비를 산출하여 주택연금의 종합적 가치를 분석하고 관련 시사점을 제공하고자 하였다. [연구방법] 본 연구는 주택연금의 장점을 계량화하여 가입 시 주택가격 대비 월지급금, 거주안정, 유산의 현재가치를 모두 합한 총 주택연금가치의 비율을 수익비로 정의하여 2019년 기준 가입연령별 주택연금의 수익비를 산정하였다. [연구결과] 주택연금의 수익비를 산정한 결과, 모든 연령대에서 수익비가 1을 초과하는 것으로 나타나 주택연금의 사회보장적 성격이 내재되었음을 확인할 수 있었다. 또한 저 연령 가입자 일수록 수익비는 높게 나타나 저연령 가입자가 상대적으로 유리한 구조로 주택연금제도가 설계된 것을 확인할 수 있었다. [연구의 시사점] 따라서 유형의 월지급금 뿐 만 아니라 주택연금에 내재된 거주안정 및 유산의 가치 등 주택연금의 종합적인 가치를 면밀히 고려하여 합리적인 가입의사결정을 할 필요가 있다. [Purpose] Korean are reluctant to join the reverse mortgage as they are unsatisfied for the level of monthly payment even though the reverse mortgage provides various benefits. In this paper, we conduct money’s worth analysis in order to deal with reasons why they do not prefer to join reverse mortgage in Korea. [Methodology] We define the total value of reverse mortgage which includes the ratio of property value and monthly payment, the residential stability and the present value of inheritance. And then we calculate the money’s worth ratio of reverse mortgage by borrower’s age as of 2019. [Findings] Our results show that the money’s worth ratio for all ages was calculated more than 1, confirming that the characteristics of social security is inherent in the reverse mortgage. Additionally, the younger member joins the reverse mortgage, the higher money’s worth ratio are provided in our results. That is, the reverse mortgage is designed with a relatively favorable structure for younger borrowers. [Implications] Thus, peoples need to decide rationally by considering aggregate value of reverse mortgage which consists of not only monthly payment but also the residential stability and inheritance value.

동의보감에 수재된 오계(烏鷄)에 대한 생리활성 연구

김진우 ( Jin Woo Kim ),심부용 ( Boo Yong Sim ),최학주 ( Hak Joo Choi ),이해진 ( Hea Jin Lee ),김동희 ( Dong Hee Kim ) 대한본초학회 2015 大韓本草學會誌 Vol.30 No.5

Objectives: The aim of this study is to investigate cell viability, anti-inflammatory, antioxidant, immunoenhancing activity using various extracts of Yeonsan Ogye. Methods: In order to evaluate cytotoxicity, MTT assay was performed. We investigated production levels of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-6, and nitric oxide(NO) in LPS-induced RAW 264.7 cells. NO production in RAW 264.7 cells was measured by using Griess reagent. Cytokines including IL-6 and TNF-α were measured by Luminex and ROS was measured by Flow cytometry. Results: No cytotoxicity of various extracts of Yeonsan Ogye was observed in RAW 264.7 cells. Productions of ROS in RAW 264.7 cells were increased from extraction of bones and decreased from extraction of skin. Also, productions of NO in RAW 264.7 cells were increased to bone extract and decreased at skin extract. In addition, productions of pro-inflammatory cytokines (IL-6 and TNF-α) in LPS-induced RAW 264.7 cells were decreased at skin, meat extracts, respectively. Finally, the levels of immune-related cytokines (IL-6 and TNF-α) were increased compared to those of the normal group. Conclusions: It is concluded that Yeonsan Ogye extracts seem to have significant biological activities likes anti-inflammatory, antioxidant, immuno-enhancing etc. These results may be developed as a raw material for new health food and new therapeutics to ease the symptoms related with inflammatory and oxidative stress. In terms of oriental traditional medicine, we expect that it contribute to building of EBM (Evidence-Based Medicine) from the this result.

언론의 정파성과 권력 개입: 1987년 이후 13~17대 대선캠페인 기간의 주요일간지 사설 분석

최진호 ( Jin Ho Choi ),한동섭 ( Dong Sub Han ) 한국지역언론학연합회 2012 언론과학연구 Vol.12 No.2

본 연구는 언론이 어떻게 정파성을 드러내면서 정치권력 창출에 개입하며 이를 심화해 나아가는지 살펴보고자 하였다. 민주화 이후 치러진 13∼17대 대선기간의 주요일간지 사설을 통시적으로 분석하여 언론의 정치지형과 변동과정을 추적하고 그 함의를 찾아보았다. 연구결과, 시간이 지날수록 언론은 지면을 통해 권력창출과정에 보다 적극적으로 개입하는 것을 확인할 수 있었다. 이념적 성향은 보수와 진보로 점차 나뉘어져 가는데, 조선일보와 한겨레는 14대부터, 동아일보와 경향신문은 15대에 시작하여 16대부터 뚜렷해졌다. 이로 인해 16대 대선부터는 주요언론들이 보수와 진보로 극명히 대립하는 양상을 보였다. 이들 언론은 자신의 정치적 입장에 따라 지지하지 않는 유력한 상대후보를 비판하여 지지하는 특정후보에게 유리하도록 보도하였다. 언론사 소유구조의 차이와 변화, 그리고 각 정부의 언론정책이 개별언론사가 정파성을 드러내며 권력개입을 시도하는 시점과 이념적 방향 등에 영향을 미쳤을 것으로 판단된다. The purpose of this study is to explore how media intervene in political-power creation expressing their partisanship and how it is deepened. For this, we performed a time series analysis in analyzing the major daily newspapers` editorial articles during the 13-17th presidential election campaign, traced political change of media, and then explored the social implications. Findings are as follows. It has been confirmed that, as time passes, media actively intervene in political-power creation process. Ideological tendency is gradually divided into the conservative and the progressive―Chosun-ilbo, Hankyoreh from the 14th, and Dong-A, Kyunghyang -Shinmun from the 16th. From the 16th, therethrough, major newspapers showed aspect conflicting fiercely between the so-called ``conservative press`` and the ``progressive press``. These media either criticize the opposite candidate or support the specific candidate depending on political stance. Based on such findings, we discuss that both the temporal point of intervention in political-power and ideological direction are affected by the structure of media ownership and the press policy of government.

조혈모세포이식 환자에서 침습성 진균 감염에 대한 Micafungin의 예방 효과 및 안전성

김시현,이동건,최수미,권재철,박선희,최정현,유진홍,이성은,조병식,김유진,이석,김희제,민창기,조석구,김동욱,이종욱,민우성,박종원 대한감염학회 2010 감염과 화학요법 Vol.42 No.3

Background: Micafungin, a potent inhibitor of 1,3-β-D-glucan synthase, is a novel antifungal agent of the echinocandin class. In vitro study showed that micafungin was effective against Aspergillus species as well as Candida species, but clinical data on the prophylactic efficacy against invasive fungal infections (IFIs) other than candidiasis are still lacking. Materials and Methods: We identified 60 consecutive adult hematopoietic stem cell transplantation (HSCT) recipients who received at least 3 doses of micafungin during neutropenic period. Micafungin was started as an alternative in patients who were intolerant or had adverse events (AEs) to primary prophylactic antifungal agents. We retrospectively reviewed the medical records and analyzed the efficacy and safety of micafungin for prophylaxis against IFIs. Results: The patients either had autologous (n=9) or allogeneic (n=51: 1 syngeneic, 24 sibling, 26 unrelated donor) HSCT. Itraconazole oral solution (n=58) was the most frequently used first line antifungal agent for prophylaxis and was administered for median 11 days. The most frequent cause of switch to micafungin was vomiting (n=42). The duration of neutropenia and micafungin administration was median 13 and 12 days, respectively. A successful outcome was achieved in 45 (75%) patients. Empirical antifungal therapy was initiated in 13 (22%) patients. There were 2 cases (3.3%) of breakthrough fungal infections which comprised a probable invasive pulmonary aspergillosis and a possible invasive fungal sinusitis. There was no case of invasive candidiasis. A total of 53 (88%) patients experienced at least one AE regardless of causality during micafungin administration. The most frequent AEs were hypokalemia, vomiting, diarrhea, and elevated serum aspartate aminotransferase or alanine aminotransferase. Among the aforementioned AEs, only 1 case of diarrhea could be classified as a probable relation with micafungin when causality was assessed. There was no AEs that caused discontinuation of micafungin. Conclusions: Micafungin seems to be a safe and effective agent for prophylaxis of IFIs including aspergillosis as well as candidiasis in HSCT recipients. However, further large, prospective, and randomized comparative studies are warranted for aspergillosis.