• Title/Summary/Keyword: Model-drug distribution

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A Numerical Study on the Effects of Drug Ejection Velocity on Endovascular Thrombolysis

  • Jeong Woo Won;Rhee Kyehan
    • Journal of Biomedical Engineering Research
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    • v.26 no.3
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    • pp.157-161
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    • 2005
  • Direct injection of a fibrinolytic agent to the intraarterial thrombosis may increase the effectiveness of thrombolysis by enhancing the permeation of thrombolytic agents into the blood clot. Permeation of fibrinolytic agents into a clot is influenced by the surface pressure, which is determined by the injection velocity of fibrinolytic agents. In order to calculate the pressure distribution on the clot surface for different jet velocities (1, 3, 5 m/sec) and nozzle arrangements (1, 9, 17 nozzles), computational fluid dynamic methods were used. Thrombolysis of a clot was mathematically modeled based on the pressure and lysis front velocity relationship. Direct injection of a thrombolytic agent increased the speed of thrombolysis significantly and the effectiveness was increased as the ejecting velocity increased. The nine nozzles model showed about $20\%$ increase of the lysed volume, and the one and seventeen nozzles models did not show significant differences. The wall shear stress decreased as the number of nozzles increased, and the wall shear stress in most vessel wall was lower than 25 Pa. The results implied that thrombolysis could be accelerated by direct injection of a drug with the moderate velocity without damaging the blood vessel wall.

The Blood-Brain Barrier Permeability and Pharmacokinetics of Nitrone Based Spin Trapping Agent, $\alpha$-Phenyl-n-tert-Butyl Nitrone (PBN) in Rats (흰쥐에서 nitrone계 항산화제인 $\alpha$-phenyl-n-tert-butyl nitrone(PBN)의 뇌 투과성 및 체내동태)

  • 이나영;강영숙
    • YAKHAK HOEJI
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    • v.46 no.2
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    • pp.124-128
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    • 2002
  • The nitrone-based free radical trapping reagent, $\alpha$-phenyl-n-tert-butyl nitrone (PBN) has been proposed as therapeutic agent for stroke. We used this for model drug of development of new drug for neuroprotection. The purpose of this study was to evaluate the blood-brain barrier (BBB) permeability of PBN in Sprague-Dawly (SD) rats. The BBB transport of PBN was investigated in SD rats using internal carotid artery perfusion (ICAP) method at a rate of 4 mι/min for 15 second. We also obtained pharmacokinetic parameters of PBN using single intravenous injection technique. When we estimated BBB permeability of PBN with ICAP method, the brain volume of distribution of PBN was 60.0 $\pm$ 12.0 $\mu\textrm{g}$/ι. The brain uptake of PBN after IV injection at 120 min was 0.15 $\pm$ 0.01%ID/g. The PBN was transported to the brain through the BBB well in rats, because PBN is small molecule (MW 177) and lipid-soluble (log P 1.23) compound.

Risk Assessment and Pharmacogenetics in Molecular and Genomic Epidemiology

  • Park, Sue-K.;Choi, Ji-Yeob
    • Journal of Preventive Medicine and Public Health
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    • v.42 no.6
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    • pp.371-376
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    • 2009
  • In this article, we reviewed the literature on risk assessment (RA) models with and without molecular genomic markers and the current utility of the markers in the pharmacogenetic field. Epidemiological risk assessment is applied using statistical models and equations established from current scientific knowledge of risk and disease. Several papers have reported that traditional RA tools have significant limitations in decision-making in management strategies for individuals as predictions of diseases and disease progression are inaccurate. Recently, the model added information on the genetic susceptibility factors that are expected to be most responsible for differences in individual risk. On the continuum of health care, from diagnosis to treatment, pharmacogenetics has been developed based on the accumulated knowledge of human genomic variation involving drug distribution and metabolism and the target of action, which has the potential to facilitate personalized medicine that can avoid therapeutic failure and serious side effects. There are many challenges for the applicability of genomic information in a clinical setting. Current uses of genetic markers for managing drug therapy and issues in the development of a valid biomarker in pharmacogenetics are discussed.

Distribution of Antibiotic Resistant Microbes in Aquaculture Effluent and Disinfection by Electron Beam Irradiation (양식장 배출수중의 항생제 내성균 분포 및 전자빔 살균처리)

  • Jang, Eun-Hee;Lim, Seung-Joo;Kim, Tak-Hyun
    • Journal of Korean Society of Environmental Engineers
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    • v.33 no.7
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    • pp.492-500
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    • 2011
  • Antibiotic resistant microbes were isolated in catfish, trout, eel and loach aquaculture effluent. The distribution of antibiotic resistant microbes in aquaculture effluent and the disinfection efficiency of antibiotic resistant microbes by electron beam irradiation were investigated. It was shown that the multi-drug resistant bacteria were Aeromonas sp., Citrobacter sp., Bacillus sp., Marinobacter sp., Pantoea sp., Pseudomonas sp. and Enterobacter sp. in aquaculture effluent. 41.7% of total strains showed the resistance against one antibiotic agent, and 58.3% of total strains showed the resistance against more than two antibiotics. It was evidently shown that the toxicity and physicochemical properties of antibiotics can be estimated using Quantitative Structure Analysis Relationship (QSAR). Electron beam irradiation was very effective for the disinfection of antibiotic resistant bacteria from aquaculture effluent, in which the disinfection efficiency was approximately 99.9% with electron beam of 1 kGy.

Effect of PVP on the Physical Stability of O/W Emulsion (O/W 유제의 물리적 안정성에 대한 PVP의 영향)

  • Oh, In-Joon;Lee, Mi-Young;Lee, Jeong-Min;Lee, Yong-Bok;Shin, Sang-Chul;Choi, Bo-Guil;Kim, Chong-Kook
    • Journal of Pharmaceutical Investigation
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    • v.27 no.4
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    • pp.287-293
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    • 1997
  • To make a stable o/w emulsion, the effects of egg lecithin as an emulsifier and polyvinylpyrrolidone (PVP) as an auxiliary emulsifier on the physical stability of emulsion were investigated. The oil-in-water emulsion system was manufactured by microfluidizer and evaluated the physical stability. Average particle size and size distribution of emulsion was measured by dynamic light scattering analyzer and interfacial tension was measured. From the interfacial tension tested, critical micelle concentration of the egg lecithin was 0.1 %w/v and optimal concentration for the preparation of emulsion was 1.0 %w/v. The mean particle size was about $0.2\;{\mu}m$ which was suitable for injections. The short-term accelerated stability studies were conducted by centrifugation, freeze-thaw method and shaking of the emulsion samples. The addition of PVP was caused the reduction in the particle size and improved the physical stability of emulsion. These results suggested that a mixed interfacial film comprising the egg lecithin and PVP was formed at the o/w interface and it was effective in preventing phase separation under thermic or mechanical stress. We used antineoplaston A10 (A10) as a model drug which is peptide and amino acid derivative having a action to the living organism against the development of neoplastic growth by a nonimmunological progress. It has a poor solubility in water and there may be a difficulty in formulation of A10. Emulsion formulation study about A10 was performed. Solubility of A10 in emulsion was about five times as high as that in water. From the results of solubility and partition coefficient, almost A10 molecules in o/w emulsion exist in the interface between oil and water.

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Bioavailability of Ranitidine Tablets in Rats (흰쥐에서 라니티딘제제의 생체이용률)

  • 이미숙;구영순
    • YAKHAK HOEJI
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    • v.39 no.6
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    • pp.636-644
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    • 1995
  • Comparison of bioavailabflity (BA) of three brands of ranitidine (RT) tablets has been studied m rats. The purpose of this study was to characterize the pharniacolunetics of RT tablets in the rat and to coinpare phannacolunetic parameters of three brands of RT tablets. In addition, it was investigated whether plasma RT concentrations m humans can be predicted from pharmacokinetic parameters obtained in rats. RT was administered intravenously in dose of RT.HCI 10mg/kg and orally in dose of RT.HCI 50mg/kg as solution or crushed sample of thablets. Plasma RT concentrations were determned by HPLC. Plasma RT concentrations as a function of time were fitted to two compartment model. Plasma RT concentrations declined with a terminal half life ($t_{{1}/2{\betha}}$) of 40.9 min. The plasma RT concentration-time curve showed two peak plasma concentrations following an oral administration of solution or crushed sample in rats like humans. No significant difference among pharmacokinetic parameters was observed except $T_{max2}$ (p<0.05). The BA for crushed sample A, B and C were found to be 54.6 40.7 and 40.0%, respectively. Equivalence of $C_{max1}$ and $T_{max2}$ were guaranteed in this study. However, it was concluded that three brands of RT tablets are bioequivalent, taking the following characteristics of RT into consideration;(1) rapid onset of the effect is not required, (2) $C_{max1}$ and $T_{max2}$ do not seem to influence the effectiveness of the drug during a long-term treatment by the usual administration of twice a day. Results from this study were combined with plarmacokinetic data for RT in dogs and humans to develop a basis for interspecies scale-up of the disposition characteristics of the drug. there were similarities in the general disposition of the drug. Allometric relationships were sought between pharmacokinetic parameters nd species body weight. Significant interspecies correlations were found for total body clearance($Cl_{t}$) and steady state volume of distribution ($Bd_{ss}$). Thus, plasma RT concentrations in humans can be predicted from pharmacokinetic parameters obtained in rats.

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Modeling and Simulation of Scheduling Medical Materials Using Graph Model for Complex Rescue

  • Lv, Ming;Zheng, Jingchen;Tong, Qingying;Chen, Jinhong;Liu, Haoting;Gao, Yun
    • Journal of Information Processing Systems
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    • v.13 no.5
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    • pp.1243-1258
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    • 2017
  • A new medical materials scheduling system and its modeling method for the complex rescue are presented. Different from other similar system, first both the BeiDou Satellite Communication System (BSCS) and the Special Fiber-optic Communication Network (SFCN) are used to collect the rescue requirements and the location information of disaster areas. Then all these messages will be displayed in a special medical software terminal. After that the bipartite graph models are utilized to compute the optimal scheduling of medical materials. Finally, all these results will be transmitted back by the BSCS and the SFCN again to implement a fast guidance of medical rescue. The sole drug scheduling issue, the multiple drugs scheduling issue, and the backup-scheme selection issue are all utilized: the Kuhn-Munkres algorithm is used to realize the optimal matching of sole drug scheduling issue, the spectral clustering-based method is employed to calculate the optimal distribution of multiple drugs scheduling issue, and the similarity metric of neighboring matrix is utilized to realize the estimation of backup-scheme selection issue of medical materials. Many simulation analysis experiments and applications have proved the correctness of proposed technique and system.

Which is the More Important Factor for Users' Adopting the Serious Games for Health? Effectiveness or Safety (건강 기능성 게임의 확산을 위한 유통 전략 연구: 유효성과 안전성에 대한 사용자 인식을 중심으로)

  • Yong-Young Kim
    • Journal of Industrial Convergence
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    • v.21 no.9
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    • pp.23-32
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    • 2023
  • Interest in Serious Games for Healthcare (SGHs) that can improve health through games is increasing. Digital Therapeutics (DTx) is a treatment that must be approved for effectiveness and safety, so it should follow the traditional drug distribution method, but SGHs are wellness products that are more flexible in terms of adoption and diffusion than DTx. SGHs are effective because it can provide customized services through continuous monitoring and feedback. When SGHs are applied to cognitive impairment treatment or behavioral correction, malfunctions and side effects are minor. This study developed research model based on the Valence Framework, gathered data from 142 undergraduates, and demonstrated that only the perceived benefits have a statistically significant positive (+) effect on SGHs acceptance intentions. Based on these results, this study suggests that SGHs companies should promote benefits in accepting SGHs for general users and they need for a distribution and analytics platform strategy based on a data-driven approach.

The Survey of Cold Storage Temperature and Determine of Appropriate Statistics Probability Distribution Model (국내 식품냉장창고 온도분포 분석 및 적정 확률분포모델 설정)

  • Kim, Hyong-Tae;Kim, Sang-Kyu;Behk, Ok-Jin;Bahk, Gyung-Jin
    • Journal of Food Hygiene and Safety
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    • v.27 no.3
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    • pp.312-316
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    • 2012
  • This study was to present the proper probability distribution models that based on the data for surveys of food cold storage temperatures as the input variables to the further MRA (Microbial risk assessment). The temperature was measured by directly visiting 7 food plants. The overall mean temperature for food cold storages in the survey was $2.55{\pm}3.55^{\circ}C$, with 2.5% of above $10^{\circ}C$, $-3.2^{\circ}C$ and $14.9^{\circ}C$ as a minimum and maximum. Temperature distributions by space-locations was $0.80{\pm}1.69^{\circ}C$, $0.59{\pm}1.68^{\circ}C$, and $0.65{\pm}1.46^{\circ}C$ as an upper (2.4~4 m), middle (1.5~2.4 m), and lower (0.7~1.5 m), respectively. Probability distributions were also created using @RISK program based on the measured temperature data. Statistical ranking was determined by the goodness of fit (GOF) to determine the proper probability distribution model. This result showed that the LogLogistic (-4.189, 5.9098, 3.2565) distribution models was found to be the most appropriate for relative MRA conduction.

Pharmacokinetic-Pharmacodynamic Modeling for the Relationship between Glucose-Lowering Effect and Plasma Concentration of Metformin in Volunteers

  • Lee, Shin-Hwa;Kwon, Kwang-il
    • Archives of Pharmacal Research
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    • v.27 no.7
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    • pp.806-810
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    • 2004
  • Metformin is a biguanide antihyperglycemic agent often used for the treatment of non-insulin dependent diabetics (NIDDM). In this study, the pharmacokinetics and pharmacodynamics of metformin were investigated in Korean healthy volunteers during a fasting state for over 10 h. In order to evaluate the amount of glucose-lowering effect of metformin, the plasma concentrations of glucose were measured for a period of 10 h followed by the administration of metformin (oral 500 mg) or placebo. In addition, the concentration of metformin in blood samples was determined by HPLC assay for the drug. All volunteers were consumed with 12 g of white sugar 10 minutes after drug intake to maintain initial plasma glucose concentration. The time courses of the plasma concentration of metformin and the glucose-lowering effect were analyzed by nonlinear regression analysis. The estimated $C_{max}$, $T_{max}$, $CL_{t}$/F (apparent clearance), V/F(apparent volume of distribution), and half-life of metformin were 1.42$\{pm}$0.07 $\mu\textrm{g}$/mL, 2.59$\{pm}$0.18h, 66.12$\{pm}$4.6 L/h, 26.63 L, and 1.54 h respectively. Since a significant counterclock-wise hysteresis was found for the metformin concentration in the plasma-effect relationship, indirect response model was used to evaluate pharmacodynamic parameters for metformin. The mean concentration at half-maximum inhibition $IC_{50}$, $k_{in}$, $k_{out}$ were 2.26 $\mu\textrm{g}$/mL, 83.26 $H^{-1}$, and 0.68 $H^{-1}$, respectively. Therefore, the pharmacokinetic-pharmacodynamic model may be useful in the description for the relationship between plasma concentration of metformin and its glucose-lowering effect.