• Title/Summary/Keyword: three-compartment model

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럼핑법을 이용한 생리학 기반 약물동태모델 및 구획화 약물동태모델 상호 호환 연구: 보리코나졸 적용 연구 (Compatibility Study between Physiologically Based Pharmacokinetic (PBPK) and Compartmental PK Model Using Lumping Method: Application to the Voriconazole Case)

  • 류효정;강원호;채정우;윤휘열
    • 한국임상약학회지
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    • 제31권2호
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    • pp.125-135
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    • 2021
  • Background: Generally, pharmacokinetics (PK) models could be stratified into two models. The compartment PK model uses the concept of simple compartmentalization to describe complex bodies, and the physiologically based pharmacokinetic (PBPK) model describes the body using multi-compartment networking. Notwithstanding sharing a theoretical background in both models, there was still a lack of knowledge to enhance compatibility in both models. Objective: This study aimed to evaluate the compatibility among PBPK, lumping model and compartment PK model with voriconazole PK case study. Methods: The number of compartments and blood flow on each tissue in the PBPK model were modified using the lumping method, considering physiological similarities. The concentration-time profiles and area under the concentration-time curve (AUC) parameters were simulated at each model, assuming taken voriconazole oral 400 mg single dose. After that, those mentioned PK parameters were compared. Results: The PK profiles and parameters of voriconazole in the three models were similar that proves their compatibility. The AUC of central compartment in the PBPK and lumping model was within a 2-fold range compared to those in the 2- compartment model. The AUC of non-eliminating tissues compartment in the PBPK model was similar to those in the lumping model. Conclusion: Regarding the compatibility of the three PK models, the utilization of the lumping method was confirmed by suggesting its reliable PK parameters with PBPK and compartment PK models. Further case studies are recommended to confirm our findings.

Simulating the Response of a 10-Storey Steel-Framed Building under Spreading Multi-Compartment Fires

  • Jiang, Jian;Zhang, Chao
    • 국제초고층학회논문집
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    • 제7권4호
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    • pp.389-396
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    • 2018
  • This paper presents a numerical investigation on the structural response of a multi-story building subjected to spreading multi-compartment fires. A recently proposed simple fire model has been used to simulate two spreading multi-compartment fire scenarios in a 10-story steel-framed office building. By assuming simple temperature rising and distribution profiles in the fire exposed structural components (steel beams, steel column and concrete slabs), finite element simulations using a three-dimensional structural model has been carried out to study the failure behavior of the whole structure in two multi-compartment fire conditions and also in a standard fire condition. The structure survived the standard fire but failed in the multi-compartment fire. Whilst more accurate fire models and heat transfer models are needed to better predict the behaviors of structures in realistic fires, the current study based on very simple models has demonstrated the importance and necessity of considering spreadingmulti-compartment fires in fire resistance design of multi-story buildings.

공기중 I-131 농도 감시에 의한 갑상선 피폭 평가법의 적용성 (Assessment of Thyroid Dose Evaluation Method by Monitoring of I-131 Concentration in Air)

  • 이종일;서경원
    • Journal of Radiation Protection and Research
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    • 제19권1호
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    • pp.69-80
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    • 1994
  • 공기중방사성요드 농도로부터 체내피폭선량을 간편하게 평가할 수 있는 전산프로그램 TCMI(Three-Compartment Model for iodine)를 개발하였다. 이 프로그램은 국제방사선방어위원회 권고 54(ICRP Publ. 54)의 3격실모델 및 호흡기모델에 따라 작업시간과 작업장의 공기중 방사성요드 농도로부터 갑상선부하량, 선량당량, 예탁선량당량 및 뇨를 통한 배출율을 시간의 함수로 평가한다. TCMI 코드를 이용함으로써 급성, 만성 및 급만성 등 구체적 피폭형태에 따른 갑상선부 하량과 선량당량 그리고 뇨를 통한 배출율을 평가하여 체내피폭평가의 적용성을 검토하였다. 또한 공기중 I-131 농도와 작업시간에 따른 갑상선부하량과 피폭선량을 간편하게 평가할 수 있는 식과 표를 제시하였다.

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승용차 탑승부내의 난방, 냉방 및 성애제거 모드에 대한 3차원 유동해석 (3-D Numerical Simulation of Flows Inside a Passenger Compartment of a Model Vehicle foer Hearting, Air-Conditioning and Defrosting Modes)

  • 허남건;조원국
    • 한국자동차공학회논문집
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    • 제1권2호
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    • pp.60-68
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    • 1993
  • Flows inside a passenger compartment of a 1/5 scale model vehicle have been simulated by using a general purpose FVM code, TURBO-3D. Three HVAC modes of heating, air-conditioning, and defrosting are simulated by defining three different inlets. Comparisons are made with the published experimental and computational results, giving a good agreement. A method of predicting the defrosting contours on the wind shield is also proposed in the present study, which enables design modifications in design stages.

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PREDICTION OF THE TRITIUM CONCENTRATION IN THE SOIL WATER AFTER THE OPERATION OF WOLSONG TRITIUM REMOVAL FACILITY

  • CHOI HEUI-JOO;LEE HANSOO;SUH KYUNG SUK;KANG HEE SUK
    • Nuclear Engineering and Technology
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    • 제37권4호
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    • pp.385-390
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    • 2005
  • The effect of the Wolsong Tritium Removal Facility on the change of tritium concentration in the soil water was assessed by introducing a dynamic compartment model. For the mathematical modeling, the tritium in the environment was thought to come from two different sources. Three global tritium cycling models were compared with the natural background concentration. The dynamic compartment model was used to model the behavior of the tritium from the nuclear power plants at the Wolsong site. The source term for the dynamic compartment model was calculated with the dry and wet deposition rates. The area around the Wolsong nuclear power plants was represented by the compartments. The mechanisms considered in deriving the transfer coefficients between the compartments were evaporation, runoff, infiltration, hydrodynamic dispersion, and groundwater flow. We predicted what the change of the tritium concentration around the Wolsong nuclear power plants would be after future operation of the tritium removal facility to show the applicability of the model. The results showed that the operation of the tritium removal facility would reduce the tritium concentration in topsoil water quickly.

혈중 목표 농도 자동 조절기(TCI) 개발 PART1 : 약동학적 모델의 수립과 검증 (Development of Target-Controlled Infusion System in Plasma Concentration. PART1 : Establishment of Pharmacokinetic Model and Verification)

  • 안재목;길호영
    • 대한의용생체공학회:의공학회지
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    • 제23권5호
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    • pp.341-349
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    • 2002
  • 본 논문에서는 혈중 목표 농도 자동 조절기(Target-controlled infusion system. TCI)를 개발하는 것으로써, 마취의가 혈중 목표 농도를 설정하면 사용약제의 약동학적 모델링에 의해서 주입속도를 자동적으로 계산하여 마취의 깊이를 예측하는 약동학적 모델의 수립과 검증 방법을 설명한다. 정확한 약동학적 모델의 구축은 시스템의 성능에 큰 영향을 미치므로 먼저 PART 1에서는 약동학적 모델을 구축하되 3-콤파트먼트 모델과 4-콤파트먼트 모델로 해석하였다. 기존의 TCI에서 사용하고 있는 3-콤파트먼트 모델에 가상의 효과처 구획(Effect Site Compartment)을 만들고 이를 네 버내 구획으로 가정한 4-콤파트먼트 모델(Four-Compartment Model)을 수립하였고, matlab 5.0을 이용하여 비교 분석하였다. 모델은 혈중 목표 농도 주입(Plasma Targeting)과 효과처 목표 농도 주입(Effect Site Targeting), 혈중 농도 유지를 위한 주입율 계산과 기타 마취 상태를 추정하는 정보를 포함한다. 시뮬레이션의 결과를 바탕으로 4-콤파트먼트 모델을 디지털 z-변환을 거쳐 디지털시그널프로세서에 프로그램하고 TCI시스템의 적용가능성을 평가하였다. 정맥 마취용 TCI는 오동작에 대한 검증이 반드시 요구되므로 구축한 모델링에 대한 시뮬레이션의 평가 방법을 설정하였다. 기존의 TCI시스템과는 달리 약동학적 약물 전달 속도 상수(k-파라미터)를 독립적으로 조절할 수 있는 기능이 추가되어 다양한 약제의 사용이 가능할 뿐만 아니라 새로운 약동학적 모델의 개발과 평가에 기여하게 되고, 환자의 체형과 병명에 따른 약동학적 모델의 변화에 대응할 수 있게 하였다.

돼지와 랫트에서 sulfamethazine의 약물동태학 및 조직분포 (Pharmacokinetic profile and tissue distribution of sulfamethazine in pigs and rats)

  • 윤효인;박승춘;오태광;조준형;박종명
    • 대한수의학회지
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    • 제37권2호
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    • pp.291-299
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    • 1997
  • In order to establish optimal dosage schedules and withdrawal times for sulfamethazine(SMZ) in pigs, pharmacokinetic and tissue distribution experiments were conducted in pigs. For comparative purposes, tissue depletion kinetics are also studied in rats. From three pigs administered with SMZ i.v., the pharmacokinetic profile of SMZ in two pigs was adequately described by a one-compartment open model whereas that in one pig was patterned after a two-compartment open model. Volume of distribution(Vd) was 0.48~0.57 L/kg and biological half-life($t_{1/2}$) was 11.8-16.8 h. From three pigs dosed with SMZ p.o., pharmacokinetic profile was explainable with a one-compartment open model. Time to reach maximum SMZ concentration in serum (Tmax) was 2.8 h, 3.2 h and 7.5 h. Elimination half-life was 2.8-7.5 h. The descending order in concentration of SMZ was plsama > kidney > liver > lung > heart > pancreas > spleen > duodenum > ileum > brain > adipsoe tissue from three pigs sacrificed at 5h, 29h and 54h after the administration of SMZ, p.o.. The protein binding of SMZ in pigs was 55.2%($2.5{\mu}g/ml$), 71.5% ($5{\mu}g/kg$) and 71.5%($10{\mu}g/ml$). The mean systemic bioavailability (F) of SMZ p.o. was 49.1 %. Meanwhile the pharmacokinetic profile of SMZ in rats was adequately described by a one-compartment open model. Absorption of SMZ p.o. in the rat was very rapid. In conclusion, the oral optimal dosage regimen of SMZ for pigs was the initial dose of 45.7 mg/kg followed by the maintenance dose of 30.2 mg/kg for high specific pathogens to SMZ. The time to reach below the stipulated residual allowable concentration (0.1 ppm) was calculated 93 h after oral administration of 200 mg/kg recommended by manufactureres.

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Application of the new ICRP iodine biokinetic model for internal dosimetry in case of thyroid blocking

  • Kwon, Tae-Eun;Chung, Yoonsun;Ha, Wi-Ho;Jin, Young Woo
    • Nuclear Engineering and Technology
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    • 제52권8호
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    • pp.1826-1833
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    • 2020
  • Administration of stable iodine has been considered a best measure to protect the thyroid from internal irradiation by radioiodine intake, and its efficacy on thyroid protection has been quantitatively evaluated in several simulation studies on the basis of simple iodine biokinetic models (i.e., three-compartment model). However, the new iodine biokinetic model adopted by the International Commission on Radiological Protection interprets and expresses the thyroid blocking phenomenon differently. Therefore, in this study, the new model was analyzed in terms of thyroid blocking and implemented to reassess the protective effects and to produce dosimetric data. The biokinetic model calculation was performed using computation modules developed by authors, and the results were compared with those of experimental data and prior simulation studies. The new model predicted protective effects that were generally consistent with those of experimental data, except for those in the range of stable iodine administration -72 h before radioiodine exposure. Additionally, the dosimetric data calculated in this study demonstrates a critical limitation of the three-compartment model in predicting bioassay functions, and indicated that dose assessment 1 d after exposure would result in a similar dose estimate irrespective of the administration time of stable iodine.

Towards Quantitative Assessment of Human Exposures to Indoor Radon Pollution from Groundwater

  • Donghan Yu;Lee, Han-Soo
    • Journal of Korean Society for Atmospheric Environment
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    • 제17권E2호
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    • pp.43-51
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    • 2001
  • A report by the national research council in the United States suggested that many lung cancer deaths each year be associated with breathing radon in indoor air. Most of the indoor radon comes directly from soil beneath the basement of foundations. Recently, radon released from groundwater is found to contribute to the total inhalation risk from indoor air. This study presents the quantitative assessment of human exposures to radon released from the groundwater into indoor air. At first, a three-compartment model is developed to describe the transfer and distribution of radon released from groundwater in a house through showering, washing clothes, and flushing toilets. Then, to estimate a daily human exposure through inhalation of such radon for an adult. a physiologically-based pharmacokinetic(PBPK) model is developed. The use of a PBPK model for the inhaled radon could provide useful information regarding the distribution of radon among the organs of the human body. Indoor exposure patterns as input to the PBPK model are a more realistic situation associated with indoor radon pollution generated from a three-compartment model describing volatilization of radon from domestic water into household air. Combining the two models for inhaled radon in indoor air can be used to estimate a quantitative human exposure through the inhalation of indoor radon for adults based on two sets of exposure scenarios. The results obtained from the present study would help increase the quantitative understanding of risk assessment issues associated with the indoor radon released from groundwater.

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전산유체역학을 이용한 실규모 오존 접촉에서의 수리거동과 유효 체적 평가에 관한 연구 (Evaluating Effective Volume and Hydrodynamic Behavior in a Full-Scale Ozone Contactor with CFD Simulation)

  • 박노석;;;배철호;이선주
    • 상하수도학회지
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    • 제18권5호
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    • pp.656-665
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    • 2004
  • An Ozone reaction model combined with CFD(Computational Fluid Dynamics) technique was developed in this research, in the simulation of ozonation, hydrodynamic behavior as well as reaction model is important because ozone is supplied to treated water as gas ozone. In order to evaluate hydrodynamic behavior in an ozone contactor, CFD technique was applied. CFD technique elucidated hydrodynamic behavior in the selected ozone contactor, which consisted of three main chambers. Three back-mixing zones were found in the contactor. The higher velocities of water were observed in the second and third compartments than that in the first compartment. The flow of the opposite direction to the main flow was observed near the water surface. Based on the results of CFD simulation, the ozone contactor was divided into small compartments. Mass balance equations were established were established in each compartment with reaction terms. This reaction model was intended to predict dissolved ozone concentration, especially. We concluded that the model could predict favorably the mass balance of ozone, namely absorption efficiency of gaseous ozone, dissolved ozone concentration and ozone consumption. After establishing the model, we discussed the effect of concentration of gaseous ozone at inlet, temperature and organic compounds on dissolved ozone concentration.