• Title/Summary/Keyword: three-compartment model

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

  • Ryu, Hyo-jeong;Kang, Won-ho;Chae, Jung-woo;Yun, Hwi-yeol
    • Korean Journal of Clinical Pharmacy
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    • v.31 no.2
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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
    • International Journal of High-Rise Buildings
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    • v.7 no.4
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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.

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

  • Lee, Jong-Il;Seo, Kyung-Won
    • Journal of Radiation Protection and Research
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    • v.19 no.1
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    • pp.69-80
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    • 1994
  • The TCMI(Three-Compartment Model for iodine) computer code has been developed, which is based on the three-compartment model and the respiratory model recommended in ICRP publication 54. This code is able to evaluate the thyroid burden, dose equivalent, committed dose equivalent and urinary excretion rate as time-dependent functions from the input data: working time and the radioiodine concentration in air. Using the TCMI code, the time-dependent thyroid burdens, the thyroid doses and the urinary excretion rates were calculated for three specific exposure patterns : acute, chronic and periodic. Applicability as an internal dose evaluation method has been assessed by comparing the results with some operational experiences. Simple equations and tables are provided to be used in the evaluation of the thyroid burden and the resulting doses for given I-131 concentration in air and the working time.

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

  • 허남건;조원국
    • Transactions of the Korean Society of Automotive Engineers
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    • v.1 no.2
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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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    • v.37 no.4
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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.

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

  • 안재목;길호영
    • Journal of Biomedical Engineering Research
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    • v.23 no.5
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    • pp.341-349
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    • 2002
  • The target controlled infusion(TCI) pump system is a logical approach to the development of improved administration techniques of an intravenous anaesthetic agent. The principle of TCI system is based on an understanding of the pharmacokinetic properties, three or four compartment model. The TCI system is optimal and flexible control of the plasma drug concentration. But the clinical goal is always to achieve a therapeutic drug effect, not a therapeutic concentration. So we developed the algorithm to target the concentration at the site of drug effect rather than the concentration in the plasma. If impulse drug is inputted into body, the decline of plasma concentration with time is shown, resulting in the expression of the differential equation. Therefore, we must reformulate our three-compartment model as four-compartment model with the effect compartment. And we tested plasma targeting and effect targeting algorithm by computer simulation using four-compartment model. So we developed the TCI capable of applying all intravenous drugs by adjusting individual pharmacokinetic parameters independently.

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

  • Yun, Hyo-in;Park, Seung-chun;Oh, Tae-kwang;Cho, Joon-hyoung;Park, Jong-myeong
    • Korean Journal of Veterinary Research
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    • v.37 no.2
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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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    • v.52 no.8
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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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    • v.17 no.E2
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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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Evaluating Effective Volume and Hydrodynamic Behavior in a Full-Scale Ozone Contactor with CFD Simulation (전산유체역학을 이용한 실규모 오존 접촉에서의 수리거동과 유효 체적 평가에 관한 연구)

  • Park, No-Suk;Mizuno, Tadao;Tsuno, Hiroshi;Bea, Chul-Ho;Lee, Seon-Ju
    • Journal of Korean Society of Water and Wastewater
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    • v.18 no.5
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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.