의약품의 효능별 안전성·유효성 평가에 관한 조사연구(Ⅰ) : 항균제 Antiboiotics

박윤주,최기환,김동섭,박인숙,정면우,임화경,오우용,강주희,박찬웅,김주일 식품의약품안전청 2001 식품의약품안전청 연보 Vol.5 No.-

새로운 물질이 개발되어 신약으로 탄생하기까지 많은 시간과 노력, 예산이 필요하다. 최근, 우리 나라에서도, 신약캐발이 어릴고 힘든 분야이지만 새로운 신약개발을 총해 얻어지는 분가가치가 막대함을 인식, 연구에 박차를 가하 있는 실정이다. 본 연구는, 의약품 개발 선진국인 미국 FDA에서 발행하는 참고자료 중 항균제 임상편가에 대한 가이드라인 및 주요 임상적응증별 항균제 기발(지역사획회득성 폐렴, 원내감염성 계렴, 급성기관지염의 2차세균감염, 만성기지염의 급성세균성 악화, 연쇄구균에 의한 인두영 및 편도염 , 단순성 요로감염증, 복합성 요로감염증 및 신우신영, 급성 세균성 부비동옆, 항 바이러스제 개발시 전임상단계에서 고려사항, 항 바이러스제 허가와 된련 잉상적 고려사항, 카레타 괸련 혈류감염)에 있어서의 파이드라인 등의 자료를 소개함으로져, 향후 제약사의 항균제 신약개발 및 허가 신청된 의악품의 전임상차료 및 잉상시험자료의 검토 평가업무에 참고자료로 활용될 수 있을 것이다. Changing or unclear interpretations of clinical trial data needed to demonstrate the effectiveness and safety of antimicrobial drug products have a times led to confusion and frustration on the part of both applicants and division of these drug products reviewers. The FDA published guidance on desing clinical protocols, implementing, and analyzing data from clinical trials for antimicrobial drug products has been presented and additional companion guidances introduced specific issues to individual infections. This document provides applicants and reviewers with minimal information appropriate for the clinical development of routine antimicrobial drug products and identifies issues common to many antimicrobial drug applications. The agency can use the kind of information to determine whether the antimicrobial drug product under study is safe and effective in the treatment of the specific infection studied.

The Study on Association of Calcium Channel SNPs with Adverse Drug Reaction of Calcium Channel Blocker in Korean

Chung, Myeon-Woo,Bang, Sy-Rie,Jin, Sun-Kyung,Woo, Sun-Wook,Lee, Yoon-Jung,Kim, Young-Sik,Lee, Jong-Keuk,Lee, Sung-Ho,Roh, Jae-Sook,Chung, Hye-Joo The Korean Society of Applied Pharmacology 2007 Biomolecules & Therapeutics(구 응용약물학회지) Vol. No.

Rapid advances in pharmacogenomic research have provided important information to improve drug selection, to maximize drug efficacy, and to minimize drug adverse reaction. The SNPs that are the most abundant type of genetic variants have been proven as valid biomarkers to give information on the prediction of pharmacokinetic/pharmacodynamic properties of drugs based on genotype. In order to elucidate a correlation between SNPs of calcium channel encoding gene and adverse reactions of calcium channel blockers, we investigated SNPs in CACNA1C gene known as a binding site of calcium channel blocker. 96 patients with hypertension who had taken or are taking an antihypertensive drug, 1,4-dihydropyridine (DHP) were included for analysis. These patients were composed of 47 patients with adverse drug reactions (ADR) such as edema from calcium channel blockers and 49 patients without ADR as a control group. The exons encoding the drug binding sites were amplified by PCR using specific primers, and SNPs were analyzed by direct sequencing. We found that there was no SNP in the exons encoding DHP binding site, but four novel SNPs in the exon-intron junction region. However, four novel SNPs were not associated with the ADR of calcium channel blockers. In conclusion, this study showed that ADR from calcium channel blockers may not be caused by SNPs of the binding sites of calcium channel blockers in CACNA1C gene.

Effects of Malloti Cortex Water Extract , Bergenin , and Acetylbergenin on Liver Fibrosis Induced by Bile Duct Ligation in Rats

(Myeon Woo Chung),(Sub Sunoo),(Seung Hwan Kim),(Hack Seang Kim) 한국응용약물학회 2001 Biomolecules & Therapeutics(구 응용약물학회지) Vol.9 No.2

The effects of Malloti Cortex Water Extract (MCWE), bergenin (isolated as an active component from MCWE), and acetylbergenin (synthesized from acetylation of bergenin) on the liver fibrosis induced by bile duct ligation (BDL) in rats. We studied hydroxyproline (HYP) as a marker of collagen accumulation in the liver, alanine aminotransferase (s-ALT), aspartate aminotransferase (s-AST), and alkaline phosphatase (s-ALP) as serum markers of liver cell damage induced by BDL. MCWE, bergenin, and acetylbergenin decreased towards normal the accumulated levels of HYP in the liver and the elevated serum levels of s-ALT, s-AST and s-ALP The results indicate that MCWE, bergenin, and acetylbergenin ameliorated the liver damage induced by BDL in rats.

The Study on Association of Calcium Channel SNPs with Adverse Drug Reaction of Calcium Channel Blocker in Korean

( Myeon Woo Chung ),( Syrie Bang ),( Sun Kyung Jin ),( Sun Wook Woo ),( Yoon Jung Lee ),( Young Sik Kim ),( Jong Keuk Lee ),( Sung Ho Lee ),( Hye Joo Chung ),( Jae Sook Roh ) 한국응용약물학회 2007 Biomolecules & Therapeutics(구 응용약물학회지) Vol.15 No.3

Rapid advances in pharmacogenomic research have provided important information to improve drug selection, to maximize drug efficacy, and to minimize drug adverse reaction. The SNPs that are the most abundant type of genetic variants have been proven as valid biomarkers to give information on the prediction of pharmacokinetic/pharmacodynamic properties of drugs based on genotype. In order to elucidate a correlation between SNPs of calcium channel encoding gene and adverse reactions of calcium channel blockers, we investigated SNPs in CACNA1C gene known as a binding site of calcium channel blocker. 96 patients with hypertension who had taken or are taking an antihypertensive drug, 1,4-dihydropyridine (DHP) were included for analysis. These patients were composed of 47 patients with adverse drug reactions (ADR) such as edema from calcium channel blockers and 49 patients without ADR as a control group. The exons encoding the drug binding sites were amplified by PCR using specific primers, and SNPs were analyzed by direct sequencing. We found that there was no SNP in the exons encoding DHP binding site, but four novel SNPs in the exon-intron junction region. However, four novel SNPs were not associated with the ADR of calcium channel blockers. In conclusion, this study showed that ADR from calcium channel blockers may not be caused by SNPs of the binding sites of calcium channel blockers in CACNA1C gene.

Gene Expression Profiles During the Activation of Rat Hepatic Stellate Cells Evaluated by cDNA Microarray

Woo, Sun-Wook,Hwang, Kwan-Ik,Chung, Myeon-Woo,Jin, Sun-Kyung,Bang, Syrie,Lee, Sung-Ho,Lee, Sung-Hee,Chung, Hye-Joo,Sohn, Dong-Hwan 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.11

Hepatic stellate cells (HSCs) are activated by producing potentially injurious connective tissue components during hepatic fibrosis, thereby exerting a pivotal action in the development of liver fibrogenesis. The aim of this study was to investigate differences in gene expression patterns during the activation of HSCs using complementary cDNA microarrays. HSCs were isolated from normal rat livers and cultured for 0 (3 h), 3, 5 and 7 d. RNA was extracted from cultured cells at each point. The target RNA was hybridized to gene-specific sequence probes immobilized on chips. The hybridization signal was assessed using a confocal laser scanner Comparison of hybridization signals and patterns allows the identification of mRNAs that are expressed differentially. Statistical analysis was used to classify and cluster the genes according to their up- or downregulation. As a result, 33 upregulated early-stage and 36 upregulated late-stage gene candidates were identified. This time-based study revealed a number of newly discovered genes involved in fibrogenesis during the activation of HSCs.

Current status of laboratory animal resources and BIOREIN

Myeon-Woo Chung 한국실험동물학회 2016 한국실험동물학회 학술발표대회 논문집 Vol.2016 No.08

Nalbuphie의 병용투여에 의한 morphine의 내성 및 의존성 헝성 저하효과

정면우(Myeon Won Chung),임화경(Hwa Kyung Lim),전용준(Yong Joon Jeon),김혜정(Hye Jung Kim),박인숙(In Sook Park),오우용(Woo Yong Oh),왕소영(So Young Wang),박윤주(Yoonju Park),강주희(Ju Hee Kang),김동섭(Dong Sup Kim),김주일(Joo Il Kim) 대한약학회 2002 약학회지 Vol.46 No.4

Morphine has been used widely on the treatment of many types of chronic pain. However the development of tolerance to morphine by repeat application is a major problem in pain therapy: The purpose of the present study was to investigate whether combined administration of nalbuphine with morphine affects the development of tolerance to and dependence on morphine. We hypothesize that the use of nalbuphine, k-agonist may prove to be useful adjunct therapy to prevent morphine-induced undesirable effects in the management of some forms of chronic pain. Morphine (10 mg/kg) was injected to rats intraperitoneally for 5 days. The variable dose of nalbuphine (0.1,1.0 and 5.0 mg/kg) was administered (I.p.) in combination with morphine injection. The development of tolerance to morphine was assessed by measuring the antinociceptive effect with the Randall-Selitto apparatus. The development of dependence on morphine was determined by the scoring the precipitated withdrawal signs for 20 min after injection of naloxone (10 mg/kg,I.p.). Nalbuphine did not attenuate antinociceptive effect of mofhine in rats. Interesting1y; combined administration of morphine with nalbuphine (100:1) sign- nifcantly attenuated the development of morphine tolerance and dependence. These results suggest that the co-admin-istration of nalbuphine with morphine in chronic morphine treatment can be one of therapies to reduce the development of dependence on morphine.

Gene Expression Profiles During the Activation of Rat Hepatic Stellate Cells Evaluated by cDNA Microarray

Sun Wook Woo,Kwan-Ik Hwang,Myeon-Woo Chung,Sun Kyung Jin,Syrie Bang,이성호,Sung Hee Lee,정혜주,손동환 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.11

Hepatic stellate cells (HSCs) are activated by producing potentially injurious connective tissue components during hepatic fibrosis, thereby exerting a pivotal action in the development of liver fibrogenesis. The aim of this study was to investigate differences in gene expression patterns during the activation of HSCs using complementary cDNA microarrays. HSCs were isolated from normal rat livers and cultured for 0 (3 h), 3, 5 and 7 d. RNA was extracted from cultured cells at each point. The target RNA was hybridized to gene-specific sequence probes immobilized on chips. The hybridization signal was assessed using a confocal laser scanner. Comparison of hybridization signals and patterns allows the identification of mRNAs that are expressed differentially. Statistical analysis was used to classify and cluster the genes according to their up- or downregulation. As a result, 33 upregulated early-stage and 36 upregulated late-stage gene candidates were identified. This time-based study revealed a number of newly discovered genes involved in fibrogenesis during the activation of HSCs.

일개 응급센터에 내원한 외상성 혈관손상 환자의 임상적 특성

박용면 ( Yong Myeon Park ),염석란 ( Seok Ran Yeom ),정진우 ( Jin Woo Jeong ),한상균 ( Sang Kyun Han ),조석주 ( Suck Ju Cho ),류지호 ( Ji Ho Ryu ),김용인 ( Yong In Kim ),정성운 ( Sung Woon Chung ) 대한외상학회 2009 大韓外傷學會誌 Vol.22 No.1

Purpose: The mortality and the amputation rates due to vascular trauma remain high despite advanced vascular surgical techniques and supportive management. The clinical features of patients with vascular trauma have not been well studied in the Korean population. The aim of this study was to analyze the clinical characteristics of patients with vascular trauma and to develop a database and guidelines for improving the outcomes of treatment. Methods: The medical records of 37 patients with traumatic vascular injuries who had visited in an emergency center between January 2002 and December 2006 were retrospectively reviewed and statistically analyzed. Results: The mean age was 37.8 years, and the male-to-female ratio was 5.2:1. The mechanism of vascular trauma was penetrating in 18 patients and blunt in 19 patients. Upper extremities were most frequently injured (39.4%). The treatment methods were primary repair in 21 patients, exploratory laparotomies in 7, radiological interventions in 3, resections and graft interpositions of the pseudoaneurysm in 3, observations in 3 and a bypass graft in 1. Four out of the 37 patients died, and three of these who died had injuried abdominal vessels. Twenty-five of the patients recovered completely, four expired, seven had neuropathy in the course of treate-ment, one had his limb amputated, and one experienced wound necrosis. Conclusion: Peripheral vessel injuries are commonly accompanied by nerve, muscle, or tendon injuries. Patients without associated fractures or compartment syndrome had good prognosis. Although the time intervals from hospital arrival to definite treatment were the shortest among patients with blunt abdominal vascular injuries, three expired. Therefore, we offer a `critical pathway` to improve the outcomes of patients with blunt abdominal vascular injury. (J Korean Soc Traumatol 2009;22:5-11)

죽염의 약리작용 평가

정수연(Soo Youn Chung),이숙영(Sook Young Yi),류항묵(Hang Mook Rheu),양지선(Ji Sun Yang),유태무(Tae Moo Yoo),김옥희(Ok Hee Kim),노용남(Yong Nam Roh),정면우(Myeon Woo Chung),안미령(Mee Ryung Ahn),최현진(Hyun Jin Choi) 한국응용약물학회 1999 Biomolecules & Therapeutics(구 응용약물학회지) Vol.7 No.2

Bamboo salt has been used for the purpose of precaution and treatment of certain diseases including cancer. Therefore, present study was carried out to ascertain the effects of bamboo salt upon anti-cancer, anti-hypertensive, and anti-diabetic activities as well. To examine the anti-cancer activity of bamboo salt, ICR mice implanted with 1 X 10^6 cells of sarcoma 180 intraperitoneally had been treated daily with bamboo salt A, crude salt, and reagent-grade NaCl (0.2, 1.0, and 2.0 g/kg, p.o.) for 60 days using adriamycin (2 mg/kg) as a positive control. Neither survival rate nor body weight had been significantly influenced by all the treatments indicating that bamboo salt A did not exert the anti-cancer effect on ICR mice. Anti-hypertensive activity was examined in spontaneously hypertensive rats (SHR) which had been administered with bamboo salt A, crude salt, and reagent-grade NaCl (0.1, 0.5, and 1.0 % in drinking water) for 28 days using hydralazin (2 mg/kg) as a positive control. Blood pressure and heart rate were measured at 1, 3, and 4 weeks after the starting date. Significant anti-hypertensive activity was not observed in any treated group compared to the positive control group. In order to determine if bamboo salt had anti-diabetic activity, rats in which diabetes had been induced by streptozotocin (45 mg/kg, i.m.) were treated daily with bamboo salt A, crude salt, and reagent-grade NaCl (0.2, 1.0, and 2.0 g/kg, p.o.) for 28 days using insulin (50 U/kg, s.c.) as a positive control. Blood samples were taken and analyzed at 1, 2, and 4 weeks after the starting date. Bamboo salt did not cause any decreasing effect on the blood glucose levels. These results clearly demonstrated that bamboo salt A did not exert anti-cancer, anti-hypertensive, or anti-diabetic activities in the present experimental animals.