인체에서 carvedilol의 심혈관계 작용에 대한 PK/PD modeling

백인환,윤민혁,윤휘열,남진경,권광일 충남대학교 약학대학 의약품개발연구소 2007 藥學論文集 Vol.22 No.-

The objective of the present study was to determine and characterize the relationship between the cardiovascular effect and plasma concentration of carvedilol by PK/PD modeling in human. A group of 32 healthy males received oral doses of 25 mg carvedilol, and blood samples were collected thirteen times for up to 30 hours after the drug administration. The effect of carvedilol on blood pressure was measured during the same period. This experiment was analyzed using the liquid-liquid extractions of carvedilol by HPLC with fluorescence detection. Pharmacokinetics parameters of carvedilol were calculated using the two-compartment model with first-order absorption. The average value of C_(max), T_(max), CL/F (apparent clearance), V/F (apparent volume of distribution) and half-life of carvedilol were 62.74 ± 20.12 ng/ml, 1.26 ± 0.86 hrs, 94.64 ± 46.01 L/hr, 1561.78 ± 941.94 L, 12.47 hr, respectively. To explain the relationship between the cardiovascular effect and plasma concentration of carvedilol, plasma drug concentrations were linked to the observed SBP and DBP via a effect compartment with a sigmoid Emax model. The model parameters were estimated by using ADAPT Ⅱ program. This PK/PD model could describe the relationship between plasma concentrations of carvedilol and cardiovascular effect such as the aspects of decreasing blood pressure and the time delay between plasma concentration and pharmaco-dynamic data.

혈소판 응집 억제제의 효과 측정법에 대한 고찰과 지원자에서 Triflusal의 혈소판 응집 억제능 평가

이병요,장힘찬,백인환,윤휘열,권광일 충남대학교 약학대학 의약품개발연구소 2010 藥學論文集 Vol.25 No.-

The anti-platelet agent is a member of a class of pharmaceuticals that decreases platelet aggregation and inhibits thrombus formation. They are effective in the arterial circulation and widely used in primary and secondary prevention of thrombotic cerebrovascular or cardiovascular disease. As a method for estimating the effects of anti-platelet agent, platelet aggregation was conventionally measured using the optical method or the impedance method. Several alternate methods currently in development or recently developed were considered, including luminescence method, flow cytometry, laser-light scattering method, and Verify Now-P2Y12 assay. Principles, advantages, and disadvantages of the optical method, impedance method, and the other alternate platelet aggregation methods were discussed in this report. 15 human volunteers were recruited for the evaluation of the efficacy of triflusal using the optical method. After the oral administration of a single dose of 900mg, 15 subjects received eight doses administered at 24-hour intervals of 600mg triflusal. Using platelet rich-plasma from above subjects, we performed baseline platelet aggregation test induced by adenosine diphosphate(ADP), collagen, and arachidonic acid. The results of platelet aggregation test after triflusal administration were compared with the baseline study. Triflusal significantly inhibited platelet aggregation induced by ADP (33.0±21.3%) and arachidonic acid (99.1±1.2%), respectively. Therefore, we concluded that anti-platelet aggregation effect of triflusal can be studied successfully with the optical method. Each of the platelet aggregation methods has value for evaluating the effects by various mechanisms of the anti-platelet agents. The ideal method for estimating the platelet aggregation as it relates to safety and efficacy in patients treated with anti-platelet agents will need to be determined in clinical trials.

Specific and Sensitive Primers Developed by Comparative Genomics to Detect Bacterial Pathogens in Grains

Baek, Kwang Yeol,Lee, Hyun-Hee,Son, Geun Ju,Lee, Pyeong An,Roy, Nazish,Seo, Young-Su,Lee, Seon-Woo The Korean Society of Plant Pathology 2018 Plant Pathology Journal Vol.34 No.2

Accurate and rapid detection of bacterial plant pathogen is the first step toward disease management and prevention of pathogen spread. Bacterial plant pathogens Clavibacter michiganensis subsp. nebraskensis (Cmn), Pantoea stewartii subsp. stewartii (Pss), and Rathayibacter tritici (Rt) cause Goss's bacterial wilt and blight of maize, Stewart's wilt of maize and spike blight of wheat and barley, respectively. The bacterial diseases are not globally distributed and not present in Korea. This study adopted comparative genomics approach and aimed to develop specific primer pairs to detect these three bacterial pathogens. Genome comparison among target pathogens and their closely related bacterial species generated 15-20 candidate primer pairs per bacterial pathogen. The primer pairs were assessed by a conventional PCR for specificity against 33 species of Clavibacter, Pantoea, Rathayibacter, Pectobacterium, Curtobacterium. The investigation for specificity and sensitivity of the primer pairs allowed final selection of one or two primer pairs per bacterial pathogens. In our assay condition, a detection limit of Pss and Cmn was $2pg/{\mu}l$ of genomic DNA per PCR reaction, while the detection limit for Rt primers was higher. The selected primers could also detect bacterial cells up to $8.8{\times}10^3cfu$ to $7.84{\times}10^4cfu$ per gram of grain seeds artificially infected with corresponding bacterial pathogens. The primer pairs and PCR assay developed in this study provide an accurate and rapid detection method for three bacterial pathogens of grains, which can be used to investigate bacteria contamination in grain seeds and to ultimately prevent pathogen dissemination over countries.

Drosophila 의 초기 발생에 요구되는 Raf Serine/Threonine Kinase

이광열,백광현,김민경,차광열 한국유전학회 2000 Genes & Genomics Vol.22 No.1

Raf kinase is one of pivotal components in various receptor tyrosine kinase (RTK) - mediated signal transduction pathways. Our study has focused on the function of Drosophila-raf (D-raf) serine/threonine kinase in the Torso (Tor) RTK required for specification of cell fates at the embryonic poles. Using mutant embryos taking endogenous D-raf protein, we found that serine/threonine kinase activity of D-raf is required for Tor signal transduction and that human Raf-1 can substitute D-raf in this pathway. Also, we show that the N-terminal deletion of D-raf can transmit the Torso signal.

Multi-Range Approach of Stereo Vision for Mobile Robot Navigation in Uncertain Environments

Kwang Ho Park,Hyung O Kim,Moon Yeol Baek,Chang-Doo Kee 대한기계학회 2003 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.17 No.10

The detection of free spaces between obstacles in a scene is a prerequisite for navigation of a mobile robot. Especially for stereo vision-based navigation. the problem of correspondence between two images is well known to be of crucial importance. This paper describes multi-range approach of area-based stereo matching for grid mapping and visual navigation in uncertain environment. Camera calibration parameters are optimized by evolutionary algorithm for suc­cessful stereo matching. To obtain reliable disparity information from both images, stereo images are to be decomposed into three pairs of images with different resolution based on measurement of disparities. The advantage of multi-range approach is that we can get more reliable disparity in each defined range because disparities from high resolution image are used for farther object a while disparities from low resolution images are used for close objects. The reliable disparity map is combined through post-processing for rejecting incorrect disparity information from each disparity map. The real distance from a disparity image is converted into an occupancy grid representation of a mobile robot. We have investigated the possibility of multi-range approach for the detection of obstacles and visual mapping through various experiments.

Pharmacokinetic/pharmacodynamic Modeling of the Cardiovascular Effects of Beta Blockers in Humans

Baek, In-Hwan,Yun, Min-Hyuk,Yun, Hwi-Yeol,Kwon, Kwang-Il 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.6

Pharmacokinetic-pharmacodynamic (PK/PD) analysis is useful study in clinical pharmacology, also PK/PD modeling is major tools for PK/PD analysis. In this study, we sought to characterize the relationship between the cardiovascular effects and plasma concentrations of the beta blocker drugs carvedilol and atenolol using PK/PD modeling in healthy humans. One group received oral doses of atenolol (50 mg) and the other group received oral doses of carvedilol (25 mg). Subsequently, blood samples were taken, and the effects of the drugs on blood pressure were determined. Plasma concentrations of drugs were measured by HPLC, and PK/PD modeling performed by applied biophase model, plasma drug concentrations were linked to the observed systolic blood pressure (SBP) and diastolic blood pressure (DBP) via an effect compartment. The model parameters were estimated using the ADAPT II program. In PK/PD analysis, it was observed the time delay between plasma concentration and effect and the time delay between SBP and DBP. The two time delays were properly explained by PD parameter "$K_{eo}$" in applied biophase model. As conclusion, the biophase PK/PD model described the relationship between the plasma concentrations of the drugs and the cardiovascular effects, including the time delay between systolic blood pressure and diastolic blood pressure.

Evaluation of the Bioequivalence of Two Brands of Naltrexone 50 mg Tablet in Healthy Volunteers

Baek, In-Hwan,Yun, Hwi-Yeol,Kang, Won-Ku,Kwon, Kwang-Il Korean College Of Clinical Pharmacy 2006 한국임상약학회지 Vol.16 No.1

날트렉손은 ${\mu}-opioid$ 수용체에 특이적이고 선택적으로 길항작용을 나타내어 마약이나 마약성 진통제의 강한 의존성 치료에 쓰일 뿐만 아니라, 알코올 의존성 치료에도 쓰이는 약물이다. 본 연구는 날트렉손 제제인 레비아 정 (50 mg tablet, 제일약품) 을 대조약으로 하여 시험약인 명인 제약의 트락손 50 mg정의 생물학적 동등성 평가를 하기 위해 22명의 건강한 지원자를 모집하였다. 지원자를 두 군으로 나누어 1정씩 투여하였고 $2{\times}2$ 교차시험을 실시하였다. 날트렉손의 혈장 중의 농도를 정량하기 위하여 발리데이션된 LC/MS/MS를 사용하였다. 채혈 시간은 투약 전 및 투약 후 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 9, 12 시간에 걸쳐 시행하였다. 생물학적 동등성을 판정하기 위한 파라미터로 12시간까지의 혈장 중 농도 곡선 하 면적$(AUC_{12hr})$과 최고 혈중 농도 $(C_{max})$를 사용하였다. $AUC_{12hr}$의 평균은 $43.45ng{\cdot}hr/ml$ (시험약)과 $43.31ng{\cdot}hr/ml$ (대조약) 으로 관찰되었고, $C_{max}$의 경우 각각 12.01 ng/m1 (시험약)과 12.27 ng/ml (대조약)으로 관찰되었다. $AUC_{12hr}$의 경우 로그변환 한 평균치 차의 90%의 신뢰구간이 log0.95-log1.07이었고, $C_{max}$의 경우 log0.87-log1.14로 계산되어 두 항목 모두 log0.8-log1.25이어야 한다는 식품의약품 안전청과 FDA의 기준을 모두 만족시켰다. 이상의 결과를 종합하면 시험약 트락손 정 50mg 은 대조약 레비아 정 50 mg에 대하여 생물학적으로 동등한 것으로 판정되었다.

특발성혈소판감소성자반증에서 스테로이드 치료 중 발생한 카로시육종 1례

조광희,박연희,최성준,강윤구,정진행,김용각,류백렬 大韓血液學會 2002 大韓血液學會誌 Vol.37 No.1

변동비반영전력시장에서의 전력거래제도 개선방안 및 추진계획

김광인(Kwang In Kim),김용완(Yong Wan Kim),문경섭(Kyeong Seob Moon),옥기열(Ki Yeol Ok),백선희(Sun hi Baek) 대한전기학회 2006 대한전기학회 학술대회 논문집 Vol.2006 No.7

현재 운영되고 있는 변동비반영전력시장(CBP)은 2001년 4월 개설되어 구조개편 초기의 혼란을 최소화하고 2004년으로 예정된 도매전력 시장 운영되기 전까지의 과도기 운영을 목적으로 설계되었다. 이는 제한된 경쟁시장으로 전력시장의 효율성 제고와 안정적인 전력공급에 어느 정도 기여하였으며, 내재된 문제가 제기되어도 곧 도입될 차기 도매전력시장에서 개선하려고 하였다. 참여정부의 배전분할 중단결정에 따라 변동비반영전력시장의 장기운영이 불가피해지게 되었고, 전력거래소는 배전분할 중단 발표 직후인 2004년 7월부터 전력시장 제도개선 논의 시작하였으며, 2005년 말에는 개선방안 연구결과를 발표하였다. 본 논문에서는 연구결과인 개선방안과 이를 시행하기 위한 추진계획을 설명하고 있다.

A case of scrotal squamous cell carcinoma in a patient with Fanconi anemia

( Dong Yeol Oh ),( Eun Joo Baek ),( Eun Joo Park ),( Kwang Joong Kim ),( Kwang Ho Kim ) 대한피부과학회 2022 대한피부과학회 학술발표대회집 Vol.73 No.2