Carbamazepine 정제의 생물학적 동등성 시험 연구

권준택,김형기 순천향대학교 의학연구소 2009 Journal of Soonchunhyang Medical Science Vol.14 No.3

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What does the China-North Korea relationship look like in the future? : Focusing on China-North Korea Military Alliance

권준택,앨리슨 그레이프 한국동북아학회 2022 한국동북아논총 Vol.27 No.4

Since 1961, China and North Korea have been officially allied through the China-Democratic People’s Republic of North Korea Treaty of Friendship, Cooperation, and Mutual Assistance. The main goal of this treaty is to ensure mutual military assistance and protection between the two states. Today, sixty-one years later, this treaty still stands. However, the relationship between China and North Korea has been shifting over the past six decades. In 1961, China and North Korea were primarily aiming to be military partners. However, today they are shifting away from focusing on the military aspect of their relationship and moving towards putting a heavier focus on being strategic political assets to one another. This shift is being driven by changing situations in the international community, such as North Korea’s development of nuclear weapons and the escalating rivalry between the United States and China. Given the sometimes inconsistent and seemingly irrational actions of these two countries in dealing with the North Korean nuclear issue and the United Nations, people may wonder, what does the future of this relationship between China and North Korea look like? The ability of this relationship to evolve and mold itself to fit changing international situations is going to allow it to survive and strengthen for many years to come. This conclusion has been proven through qualitative research and analysis of each article contained in the Treaty of Friendship, Cooperation, and Mutual Assistance, as well as analysis of the impacts of the North Korean nuclear crisis, the United States-China rivalry, and China’s growing power.

Aceclofenac 경구제제의 생물학적 동등성 연구

권준택,김형기,손동렬,염윤기 순천향의학연구소 2004 Journal of Soonchunhyang Medical Science Vol.10 No.1

The bioequivalence of generic aceclofenac(Anacle^(®), Korea Pharma Co.) tablet to the aceclofenac tablet(Arital^(®), DaeWoong Pharmaceutical Co.) as a reference drug. Single dose of 100 mg aceclofenac was administered to 20 healthy male volunteers in a balanced, randomized crossover design with a washout between the two study periods. Blood samples were collected up to 12 hours and plasma concentration of aceclofenac was measured by well validated reverse phase high-performance liquid chromatography. Pharmacokinetic parameters were analyzed by non-compartmental analysis and ANOVA test was used for the statistical analysis of parameters. No statistically significant formulation, period, or sequence effect was encountered. Ninety percent confidence intervals of log transformed C_(max) and AUC_(t) were comprised in the stipulated 0.80-1.25 range. These results suggest that test formulation of aceclofenac is bioequivalent with the reference, both formulations in 100 mg tablet.

니코틴 대사와 CYP2A6 유전자 빈도에 관한 민족적 다형성

권준택 순천향의학연구소 2000 Journal of Soonchunhyang Medical Science Vol.6 No.2

사람의 CYP2A6 유전자는 CYP2A6*1A, CYP2A6*1B, CYP2A6*2, CYP2A6*3, CYP2A6*4 및 CYP2A6*5 대립 유전자가 밝혀져 있으며, nicotine-C 산화반응을 촉매하고 있다. 앞선 보고에 의하면, 일본인에서 nicotine 대사의 개인간 차이는 CYP2A6 유전자 다형성 (genetic polymorphism)과 관련이 있음이 증명된 바 있다. 저자는 Nicotine대사와 CYP2A6 대립 유전자들의 빈도에서 인종간의 차이를 증명하기 위해 209예의 한국인에서 nicotine대사와 CYP2A6의 유전자형을 연구하였다. Nicotine 껌을 투여 후 2시간에 혈장 cotinine/nicotine 비를 계산하여 nicotine대사의 지표로 사용하였으며, CYP2A6의 유전자형은 PCR-RFLP방법으로 결정하였다. 실험 결과 CYP2A6*1A, CYP2A6*1B, CYP2A6*4 및 CYP2A6*5 대립 유전자의 빈도는 한국인 (각각 45.7%, 42.8%, 11.0% 및 0.5%)과 일본인간에는 인종간의 차이를 보였다. 그러나 CYP2A6*2와 CYP2A6*3 대립 유전자형에는 어떠한 차이도 관찰할 수 없었다. 4명의 CYP2A6*4 homozygotes에서는 cotinine형성이 완전히 결여되었으며 그 결과는 일본인에서 관찰된 자료와 일치하였다. CYP2A6*4 heterozygotes에서는 이것이 없는 사람들에 비해 낮은 대사율을 보이는 경향이 있었으며, CYP2A6*1B 대립유전자를 지닌 사람들은 cotinine 형성 능력이 훨씬 높은 경향을 나타내었다. 니코틴 대사의 개인별 차이는 CYP2A6의 유전자 다형과 밀접한 관련이 있음을 확인하였다. 한국인에서 대사율의 probit plot 결과는 0.6의 antimode치를 보여 일본인에서 얻은 결과와 동일하였다. CYP2A6*1B/CYP2A6*4를 가진 한 명의 한국인에서 새로운 CYP2A6 돌연변이가 있는 것으로 보였다. 한국인의 probit plot 결과는 일본인보다 높은 비를 보였으며, 각 유전자형 군에서 한국인 군은 일본인 군에 비하여 유의하게 높은 대사율을 보였다. Cotinine 형성에서 인종간의 차이는 유전학적 소인 외에도 환경인자 및 식이 등의 인자들이 관여할 것으로 보인다.

특별강연 ( 1997 . 11. 14 ) : 임상약물유전학

권준택 한국응용약물학회 1997 학술대회 Vol.1997 No.2

한국인에서의 CYP2C19 유전자형의 다형성

권준택,김형기,손동렬,염윤기 순천향의학연구소 2004 Journal of Soonchunhyang Medical Science Vol.10 No.1

The S-mephenytoin 4'-hydroxylase (CYP2C19) metabolizes a number of clinically used drugs and shows a marked interethnic difference in the incidence of the poor metabolizer (PM). In the present study, we genotyped 215 healthy unrelated Koreans (64 females, aged 20-41 yr, residing in Chungcheong province) for functionally defective alleles, CYP2C19_(m1) and CYP2C19_(m2). Detection of the normal (CYP2C19_(wt)) and defective alleles was performed by polymerase chain reaction/restriction enzyme analysis. The genomic DNA was isolated from peripheral blood. The allelic frequencies of the wild-type (CYP2C19_(wt)) and CYP2C19_(m1) were 72.6% and 27.4%, and the wild-type (CYP2C19_(wt)) and CYP2C19_(m2) were 85.1% and 14.9%, respectively. For each CYP2C19_(m1) and CYP2C19_(m2), the observed numbers of three genotypes were similar to those calculated in accordance with the Hardy-Weinberg equation. The frequencies of homozygotes for CYP2C19_(m1), CYP2C19_(m2) and compound heterozygotes were 9.7%, 2.8% and 4.2%, respectively. The mutants of CYP2C19 were identified in 36 subjects (16.7%). These results suggest that frequency of mutants of CYP2C19 in Koreans resembled the Orientals rather than Caucasians.

한국인에서의 CYP2E1 유전자형

권준택,김형기,손동렬,염윤기 순천향의학연구소 2004 Journal of Soonchunhyang Medical Science Vol.10 No.1

Cytochrome P4502E1 (CYP2E1) is inducible by ethyl alcohol and activates procarcinogenic N-nitrosodimethylamine (NDMA), benzene, urethane and other lower molecular weight compound. CYP2E1 is also involved in metabolism of certain drugs, for example, alcohol, acetaminophen, tamoxifen, theophylline, fluorinated anesthetics, and chlorozoxazone. CYP2E1 activity was shown to be polymorphically distributed in humans and has been suggested to play a role in hepatocellular carcinoma and alcoholic related disorders. Although genetic predisposition to alcoholism and alcoholic liver disease has been reported, genetic susceptibility to alcoholic pancreatitis is still a matter of debate. The aims of this study were to investigate the allelic frequency of CYP2E1 Rsa I polymorphism in Koreans. We investigated the frequency distribution of CYP2E1 Rsa I polymorphism in 212 unrelated healthy Koreans and 42 hepatocellular carcinoma patients. Detection of the CYP2E1 alleles was performed by polymerase chain reaction and restriction fragment length analysis. The genomic DNA was isolated from peripheral blood with conventional phenol: chloroform extraction method. The allelic frequencies of c1 and c2 in healthy volunteers were 0.85 and 0.15, respectively. The rare type (c2/c2) of CYP2E1 Rsa I polymorphism was 0.005 in healthy volunteers.

흰쥐 간장에서 허혈-재관류에 의한 간장해 모델의 연구(1)

권준택,이종화,조병현,양훈모,박종안,김유재,김종배,차영덕,김창호 최신의학사 1992 最新醫學 Vol.35 No.12

수소연료 중 일산화탄소의 고분자전해질 연료전지에 대한 영향

권준택,김준범 한국수소및신에너지학회 2008 한국수소 및 신에너지학회논문집 Vol.19 No.4

Carbon monoxide(CO) is one of the contamination source in reformed hydrogen fuel with an influence on performance of polymer electrolyte membrane fuel cell(PEMFC). The studies of CO injection presented here give information about poisoning and recovery processes. The aim of this research is to investigate cell performance decline due to carbon monoxide impurity in hydrogen. Performance of PEM fuel cell was investigated using current vs. potential experiment, long time(10 hours) test, cyclic feeding test and electrochemical impedance spectra. The concentrations of carbon monoxide were changed up to 10 ppm. Performance degradation due to carbon monoxide contamination in anode fuel was observed at high concentration of carbon monoxide. The CO gas showed influence on the charge transfer reaction. The performance recovery was confirmed in long time test when pure hydrogen was provided for 1 hour after carbon monoxide had been supplied. The result of this study could be used as a basis of various reformation process design and fuel quality determination.

건강한 한국인 자원자에서 theophylline 약동학에 미치는 Cimetidine의 효과

권준택,채석,손동렬,염윤기,김형기 한국임상약학회 2007 한국임상약학회지 Vol.17 No.1

Theophylline은 methylxanthine계열 기관지확장제중 가장 강력하며 기관지 천식이나 만성 폐쇄성 호흡기 질환환자에서 사용된다. Theophylline은 치료지수가 5-20 mg/L로 매우 좁은 치료지수를 갖는 약물이다. Cimetidine과 theophylline은 주로 간에 존재하는 cytochrome P450 (CYP) 효소에 의해 대사되며 theophylline은 유전적 다형성이 보고된 바있는 CYP1A2에 의해 대부분 대사된다. 본 연구는 theophylline의 약동학에 미치는 cimetidine의 영향을 평가하고 CYP1A2 유전적 다형성의 영향유무를 검증하였다. 8명의 건강한 비흡연자인 한국인 자원자를 모집하여 공개, 2기 교차시험을 실시하였다. 8명의 자원자에게 1기 시험의 첫날 100 mg의 aminophylline을 경구로 단회 투여하였으며 약물투여 후 36시간까지 채혈하여 혈장을 보관하였다. 공혈장 채취를 위해 채혈한 혈액중 일부를 가지고 유전자형 검색을 실시하였다. 1주일의 휴약기를 거친 후 2기 시험을 진행하였다. 2기 시험의 첫날 같은 용량의 aminophylline과 200 mg의 cimetidine을 같이 경구로 단회 투여하였다. 혈장 중 theophylline농도는 고성능 액체 크로마토그래피를 이용하여 측정하였으며 1기와 2기 시험에서 각종 약동학적 경수를 컴퓨터를 이용하여 계산하였다. 8명의 자원자에서 PCR-RFLP를 이용하여 유전자형 검색을 실시하였다. 8명(남자 4명, 여자 4명)의 자원자에서 약물과 관련한 약물이상 반응은 시험기간동안 발생하지 않았다. 약동학적 분석에서 theophylline의 혈장 농도 곡선하 면적(AUC)와 최고혈중농도()가 cimetidine과 theophylline을 동시에 투여하였을 때 통계적으로 유의하게 증가하였으며 경구 청소율(CL/F)은 유의하게 감소하였다. 8명의 CYP1A2 유전자형 검색에서 돌연변이 유전자형은 발견하지 못하였으며 CYP1A2*1C 유전자형 검색에서 모두 (G/G) homozygote였으며 CYP1A2*1F 유전자형 검색에서는 5명이 (A/A) homozygote이고 3명이 (A/C) heterozygote였다. 따라서 theophylline대사에 CYP1A2유전자형에 따른 대사능의 차이는 관찰할 수 없었다. 이상의 결과를 요약하면 theophylline의 약동학은 cimetidine에 의해 유의한 차이를 보였으며 CYP1A2유전자형에 따른 영향은 관찰할 수 없었다. CYP1A2유전자형에 따른 생체내 대사능을 관찰하는 실험이 향후 이루어 져야 할 것으로 사료된다. The purpose of the present study was to investigate the effect of cimetidine on theophylline pharmacokinetics in Korean healthy normal subjects. Eight subjects were enrolled and open label, two period cross-over study was conducted without significant drug related adverse reactions. Cimetidine seemed that significantly inhibited the metabolism of theophylline, oral clearance decreased significantly when cimetidine was coadministered. Coadministered cimetidine increased and of theophylline. All subjects were genotyped using PCR-RFLP methods to evaluate the differences in metabolic capacity in accordance with CYP1A2 genotypes, but no mutant genotype was found. This suggests that metabolic capacities were not significantly affected by CYP1A2 genotypes among subjects. In conclusion, disposition of theophylline was significantly affected by coadministered cimetidine. Further evaluation with well-designed drug interaction study in accordance with various genotype of CYP1A2 is needed.