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Comparison of oral absorption models for pregabalin: usefulness of transit compartment model
Hong, Taegon,Han, Seunghoon,Lee, Jongtae,Jeon, Sangil,Yim, Dong-Seok Dove Medical Press 2016 Drug design, development and therapy Vol.10 No.-
<P>Pregabalin is an anticonvulsant used for the treatment of neuropathic pain and partial seizure in adults. The aim of this study was to develop a population pharmacokinetic (PK) model to describe the absorption characteristics of pregabalin given fasted or after meals. Data from five healthy subject PK studies (n=88) of single- or multiple-dose pregabalin (150 mg) were used. Pregabalin was administered twice daily, without meals or 30 min after a meal (regular or high-fat diet) in the morning and 30 min or 4 h after a meal (regular diet) in the evening. Serial plasma samples were collected up to 24 h after the last dose for PK analysis. Because the peak concentrations were not properly modeled by a conventional first-order absorption model, Erlang frequency distribution, Weibull-type absorption, and transit compartment models were tested on a two-compartment linear PK model using a nonlinear mixed-effects method (NONMEM; version 7.3). The transit compartment model best described the absorption characteristics of pregabalin regardless of meal status. We conclude that the absorption model should be carefully chosen based on the principle of model development and validation and not by following a conventional first-order absorption model for its popularity and simplicity, especially when the PK dataset includes densely sampled absorption-phase data.</P>
Hong, Taegon,Han, Seunghoon,Lee, Jongtae,Jeon, Sangil,Park, Gab-Jin,Park, Wan-Su,Lim, Kyoung Soo,Chung, Jae-Yong,Yu, Kyung-Sang,Yim, Dong-Seok Dove Medical Press 2015 Drug design, development and therapy Vol.9 No.-
<P>A single 400 mg dose of moxifloxacin has been the standard positive control for thorough QT (TQT) studies. However, it is not clearly known whether a 400 mg dose is also applicable to TQT studies in Asian subjects, including Koreans. Thus, we aimed to develop a pharmacokinetic (PK)-pharmacodynamic (PD) model for moxifloxacin, to evaluate the time course of its effect on QT intervals in Koreans. Data from three TQT studies of 33 healthy male Korean subjects who received 400 and 800 mg of moxifloxacin and placebo (water) were used. Twelve-lead electrocardiograms were taken for 2 consecutive days: 1 day to record diurnal changes and the next day to record moxifloxacin or placebo effects. Peripheral blood samples were also obtained for PK analysis. The PK-PD data obtained were analyzed using a nonlinear mixed-effects method (NONMEM ver. 7.2). A two-compartment linear model with first-order absorption provided the best description of moxifloxacin PK. Individualized QT interval correction, by heart rate, was performed by a power model, and the circadian variation of QT intervals was described by two mixed-effect cosine functions. The effect of moxifloxacin on QT interval prolongation was well explained by the nonlinear dose-response (E<SUB>max</SUB>) model, and the effect by 800 mg was only slightly greater than that of 400 mg. Although Koreans appeared to be more sensitive to moxifloxacin-induced QT prolongation than were Caucasians, the PK-PD model developed suggests that a 400 mg dose of moxifloxacin is also applicable to QT studies in Korean subjects.</P>
Kang, Taegon,Banquy, Xavier,Heo, Jinhwa,Lim, Chanoong,Lynd, Nathaniel A.,Lundberg, Pontus,Oh, Dongyeop X.,Lee, Han-Koo,Hong, Yong-Ki,Hwang, Dong Soo,Waite, John Herbert,Israelachvili, Jacob N.,Hawker, American Chemical Society 2016 ACS NANO Vol.10 No.1
<P>We describe robustly anchored triblock copolymers that adopt loop conformations on surfaces and endow them with unprecedented lubricating and antifouling properties. The triblocks have two end blocks with catechol-anchoring groups and a looping poly(ethylene oxide) (PEO) midblock. The loops mediate strong steric repulsion between two mica surfaces. When sheared at constant speeds of similar to 2.5 mu m/s, the surfaces exhibit an extremely low friction coefficient of similar to 0.002-0.004 without any signs of damage up to pressures of similar to 2-3 MPa that are close to most biological bearing systems. Moreover, the polymer loops enhance inhibition of cell adhesion and proliferation compared to polymers in the random coil or brush conformations. These results demonstrate that strongly anchored polymer loops are effective for high lubrication and low cell adhesion and represent a promising candidate for the development of specialized high-performance biomedical coatings.</P>
다결정 NiAl의 Thermomechanical Treatment에 의한 GBCD와 파괴특성의 변화
김태곤(Taegon-Kim),홍경태(Kyung Tae Hong),이경섭(Kyung Sub Lee) 대한기계학회 2001 대한기계학회 춘추학술대회 Vol.2001 No.3
A study has been made to investigate the change of GBCD(Grainboundary character distribution) and the fracture behavior of polycrystalline NiAl. For this, EBSD and the ring on ring disk bend test in conjunction with the controlled indentation flaw method are used. The crack initiated at the indentation for indentation load exceeding 196.14N. The fracture toughness was determined from an analysis of the dependence of fracture stress on indentation load. The true fracture stress was determined from measuring acoustic emission during indentation and bending test of initial NiAl, 5 times cyclic heat-treated and forged NiAl. The fracture mode of polycrystalline NiAl was primarily intergranular at room temperature. The fracture toughness was measured as 4.61 ± 1.78 (MPam<SUP>-1/2</SUP>)for initial NiAl, 6.73 ± 1.34 (MPam<SUP>-1/2</SUP>) for 5 times cyclic heat-treated NiAl and 5.8 ± 0.5 (MPam<SUP>-1/2</SUP>) for forged specimen. The fraction of special CSL(coincident site lattice) boundary was increased in the 5 times cyclic heat-treatment and low angle boundaries(LABs) were increased in forging. It was considered thatoughness was increased as rising of the fraction of special grainboundary(SGBs) and LABs to the random grainboundary(RGBs).
관개취약성 평가모형 및 군집분석을 활용한 용수공급 위험도 평가
Nam, Won-Ho,Kim, Taegon,Hong, Eun-Mi,Hayes, Michael J.,Svoboda, Mark D. 한국농공학회 2015 한국농공학회논문집 Vol.57 No.1
Because reservoirs that supply irrigation water play an important role in water resource management, it is necessary to evaluate the vulnerability of this particular water supply resource. The purpose of this study is to provide water supply risk maps of agricultural reservoirs in South Korea using irrigation vulnerability model and cluster analysis. To quantify water supply risk, irrigation vulnerability indices are estimated to evaluate the performance of the water supply on the agricultural reservoir system using a probability theory and reliability analysis. First, the irrigation vulnerability probabilities of 1,346 reservoirs managed by Korea Rural Community Corporation (KRC) were analyzed using meteorological data on 54 meteorological stations over the past 30 years (1981-2010). Second, using the K-mean method of non-hierarchical cluster analysis and pre-simulation approach, cluster analysis was applied to classify into three groups for characterizing irrigation vulnerability in reservoirs. The morphology index, watershed area, irrigated area, and ratio between watershed and irrigated area are selected as the clustering analysis parameters. It is suggested that the water supply risk map be utilized as a basis for the establishment of risk management measures, and could provide effective information for a reasonable decision making on drought risk mitigation.
주단위 표준강수증발산지수를 활용한 2014~2015년 북한의 극한 가뭄 평가
Nam, Won-Ho,Hong, Eun-Mi,Choi, Jin-Yong,Kim, Taegon,Hayes, Michael J.,Svoboda, Mark D. 한국농공학회 2017 한국농공학회논문집 Vol.59 No.4
North Korea is one of the high vulnerable countries facing the threat of natural disaster and has experienced more frequent disasters in recent years. These disasters have significantly led to food shortages and large reductions in crop yields. In 2015, both North Korean officials and international agencies had identified the extreme drought event, the worst in one hundred years according to the North Korean government. The objective of this study was an assessment of the extreme drought events in 2014~2015, and to apply climatic drought indices for drought monitoring in North Korea. Characteristics of the extreme drought in North Korea are examined by using the weekly-based Standardized Precipitation Evapotranspiration Index (SPEI). The drought characteristics illustrated by the SPEI results are compared with a Standardized Precipitation Index (SPI) results and drought impact information to understand how these indices can explain the drought conditions within the country. These results demonstrated that the SPEI could be an effective tool to provide improved spatial and temporal drought conditions to inform management decisions for drought policy.
Han, Seunghoon,Jeon, Sangil,Hong, Taegon,Lee, Jongtae,Bae, Soo Hyeon,Park, Wan-su,Park, Gab-jin,Youn, Sunil,Jang, Doo Yeon,Kim, Kyung-Soo,Yim, Dong-Seok Dove Medical Press 2015 Drug design, development and therapy Vol.9 No.-
<P>No wholly successful weight-control drugs have been developed to date, despite the tremendous demand. We present an exposure–response model of sibutramine mesylate that can be applied during clinical development of other weight-control drugs. Additionally, we provide a model-based evaluation of sibutramine efficacy. Data from a double-blind, randomized, placebo-controlled, multicenter study were used (N=120). Subjects in the treatment arm were initially given 8.37 mg sibutramine base daily, and those who lost <2 kg after 4 weeks’ treatment were escalated to 12.55 mg. The duration of treatment was 24 weeks. Drug concentration and body weight were measured predose and at 4 weeks, 8 weeks, and 24 weeks after treatment initiation. Exposure and response to sibutramine, including the placebo effect, were modeled using NONMEM 7.2. An asymptotic model approaching the final body weight was chosen to describe the time course of weight loss. Extent of weight loss was described successfully using a sigmoidal exposure–response relationship of the drug with a constant placebo effect in each individual. The placebo effect was influenced by subjects’ sex and baseline body mass index. Maximal weight loss was predicted to occur around 1 year after treatment initiation. The difference in mean weight loss between the sibutramine (daily 12.55 mg) and placebo groups was predicted to be 4.5% in a simulation of 1 year of treatment, with considerable overlap of prediction intervals. Our exposure–response model, which included the placebo effect, is the first example of a quantitative model that can be used to predict the efficacy of weight-control drugs. Similar approaches can help decision-making during clinical development of novel weight-loss drugs.</P>
Lee, Jongtae,Jeon, Sangil,Hong, Taegon,Han, Seunghoon,Yim, Dong-Seok Springer 2015 European journal of clinical pharmacology Vol.71 No.11
<P>This study aimed to determine the effect of PET scan timings on the reliability of occupancy parameter estimates and to identify the scan timing design that gives the most reliable occupancy parameter estimates.</P>