• Title/Summary/Keyword: Compartment Model

Search Result 315, Processing Time 0.029 seconds

Bioequivalence and Pharmacokinetic study of Gabapentin 300mg Capsules using Liquid Chromatography-Tandem Mass Spectrometry (LC/MS/MS) in Volunteers (LC/MS/MS를 이용한 가바펜틴 300 mg 캡슐의 성인 지원자에 대한 생물학적 동등성 및 약물동태 연구)

  • Jeong, Ji-Hoon;Kwon, Jun-Tack;Yun, Hwi-Yeol;Kang, Won-Ku;Kwon, Kwang-Il
    • Korean Journal of Clinical Pharmacy
    • /
    • v.16 no.1
    • /
    • pp.63-68
    • /
    • 2006
  • Gabapentin, 1-(aminomethyl-1-cyclohexyl)acetic acid, is anew antiepileptic drug related to ${\gamma}-aminobutyric$ acid(GABA) currently being introduced in therapy worldwide. The bioavailability and pharmacokinetics of gabapentin capsules were examined in 22 volunteers who received a single oral dose in the fasting state by randomized balanced $2{\times}2$ crossover design. After dosing, blood samples were collected for a period of 24 hours and analyzed by liquid chromatography-tandem mass spectrometry (LC/MS/MS). Time course of plasma gabapentin concentration was analyzed with non-compartmental and compartmental approaches. $WinNonlin^{(R)}$, the kinetic computer program, was used for compartmental analysis. One compartment model with first-order input, first-order output with no lag time and weighting by $1/(predieted\;y)^2$ was chosen as the most appropriate pharmacokinetic model for the volunteers. The major pharmacokinetic parameters $(AUC_{0-24hr},\;AUC_{inf},\;C_{max}\;and\;T_{max})$ and other parameters $(K_a,\;K_{el},\;V_d/F\;and\;Cl/F)$ of $Gapentin^{TM}$ (test drug) and $Neurontin^{TM}$ (reference drug) were estimated by non-compartmental analysis and compartmental analysis. The 90% confidence intervals of mean difference of logarithmic transformed $AUC_{0-24hr}\;and\;C_{max}$ were $log(0.9106){\sim}log(1.l254)\;and\;log(0.8521){\sim}log(1.0505)$, respectively. It shows that the bioavailability of the test drug is equivalent with that of the reference drug. There was no statistically significant difference between the two drugs in all pharmacokinetic parameters.

  • PDF

An Arachidonic Acid Metabolizing Enzyme, 8S-Lipoxygenase, in Mouse Skin Carcinogenesis

  • Kim Eun-Jung
    • Nutritional Sciences
    • /
    • v.9 no.3
    • /
    • pp.212-226
    • /
    • 2006
  • The involvement of arachidonic acid (AA) metabolizing enzyme, lipoxygenase (LOX), in the development of particular tumors in humans has gradually been acknowledged and LOX has emerged as a novel target to prevent or treat human cancers. In the mouse skin carcinogenesis model, which provides an excellent model to study multistage nature of human cancer development, many studies have shown that some of the LOXs are constitutively upregulated in their expression. Moreover, application of LOX inhibitors effectively reduced tumor burdens, which implicates the involvement of LOX in mouse skin tumor development as well. 8S-LOX is a recently cloned LOX, which is specifically expressed in mouse skin after 12-O-tetradecanoyl-phorbol-13-acetate (TPA) treatment but not in normal skin. Unlike other members of the LOX 'family' expressed in mouse skin, this TPA-induced expression of 8S-LOX is prominent only in the skin of the TPA tumor promotion-sensitive strains of mice (SENCAR, CD-1, and NMRI) but not in the promotion-resistant C57BL/6J mice. This is a very unique phenomenon among strains of mice. Constitutive upregulation of 8S-LOX was also found in early stage papillomas and the expression was gradually reduced as the tumors became malignant. Based on these observations, it has been thought that 8S-LOX is involved in TPA-induced tumor promotion as well as in tumor conversion from papillomas to carcinomas. In accordance with this hypothesis, several studies have suggested possible roles of 8S-hydroxyeicosatetraenoic acid (HETE), an AA metabolite of 8S-LOX, in mouse skin tumor development. A clastogenic activity of 8S-HETE was demonstrated in primary keratinocytes and a close correlation between the levels of etheno-DNA adducts and 8S-HETE during skin carcinogenesis was also reported. On the other hand, it has been reported that 8S-LOX protein expression is restricted to a differentiated keratinocyte compartment Moreover, reported findings on the ability of 8S-HETE to cause keratinocyte differentiation appear to be contrary to the procarcinogenic features of the 8S-LOX expression, presenting a question as to the role of 8S-LOX during mouse skin carcinogenesis. In this review, molecular and biological features of 8S-LOX as well as current views on the functional role of 8S-LOX/8S-HETE during mouse skin carcinogenesis are presented.

A Numerical Study of Radiation Effect under Smoke Movement in Room Fire (실내화재에서 연기거동에 미치는 복사영향에 대한 수치해석적 연구)

  • 정진용;유홍선;홍기배
    • Fire Science and Engineering
    • /
    • v.14 no.3
    • /
    • pp.6-12
    • /
    • 2000
  • This paper describes the smoke movement of a fire field model based on a self-developed SMEP(Smoke Movement Estimating Program) code to the simulation of fire induced flows in the two types of compartment space containing the radiation effect under smoke movement in room fire. The SMEP using PISO algorithm solves conservation equations for mass, momentum, energy and species, together with those for the modified k-$\varepsilon $ turbulence model with buoyancy term. Also it solves the radiation equation using the discrete ordinates method. The result of the calculated smoke temperature containing radiation effect has shown reasonable agreement compared with the experimental data. On the other hand, a difference of a lot was found between the temperature predicted by the SMEP with only convection effect and obtained by the experimental result. This seems to come from the radiation effect of $H_2$O and $CO_2$ gas under smoke productions. Thus, the consideration of the radiation effect under smoke in fire may be necessary in order to produce more realistic result.

  • PDF

Comparative Bioavailability and Metabolism of Two Capsule Formulations of Fluoxetine in Human Volunteers (플루옥세틴 캅셀제의 지원자에 대한 생체이용율 및 대사율 비교)

  • Kang, Won-Ku;Park, Yong-Soon;Cho, Gyu-Haeng;Choi, Jun-Sik;Kwon, Kwang-Il
    • YAKHAK HOEJI
    • /
    • v.42 no.5
    • /
    • pp.513-518
    • /
    • 1998
  • Fluoxetine is a nontricyclic antidepressant which blocks serotonin reuptake selectively. Its N-demethyl metabolite, norfluoxetine is also selective inhibitor of serotonin uptake . This study was carried out to compare the bioavailability of Myung-in fluoxetine (20mg/cap.) with that of Prozac$^{\circde{R}}$. The bioavailability was conducted on 24 healthy volunteers who received a single dose (80mg) of each drug in the fasting state, in a randomized balanced 2-way crossover design. After closing, serial blood samples were collected for a period of 48 hours, Plasma was analyzed for fluoxetine and norfluoxetine by a sensitive and validated HPLC assay. The major pharmacokinetic parameters ($AUC_{0-48\;hr}$, Cmax, Tmax , $AUC_{inf.}$, MRT. $T_{1/2}$, Vd and Cl) were, calculated from the plasma fluoxetine concentration-time data of each volunteer. The microcomputer program, 'WinNonlin' was used for compartmental analysis. A two-compartment model with first-order input, first-order output and no lag time was chosen as the most appropriate pharmacokinetic model. The data were best described by using a weighting factor of $1/y^2$. Though the plasma fluoxetine concentrations of Myung-in fluoxetine were higher than those of Prozac$^{\circde{R}}$ at all observed time from 7.9% to 16.9% (P<0.05 at 6.7 and 10 hr), the bioavailability of Myung-in fluoxetine appeared to be bioequivalent with that of Prozac$^{\circde{R}}$. There were no statistical significant differences between the two drugs in all pharmacokinetic parameters including $AUC_{0-48\;hr}$ of norfluoxetine.

  • PDF

Evaluation on Sensitivity and Approximate Modeling of Fire-Resistance Performance for A60 Class Deck Penetration Piece Using Heat-Transfer Analysis and Fire Test

  • Park, Woo Chang;Song, Chang Yong
    • Journal of Ocean Engineering and Technology
    • /
    • v.35 no.2
    • /
    • pp.141-149
    • /
    • 2021
  • The A60 class deck penetration piece is a fire-resistance apparatus installed on the deck compartment to protect lives and to prevent flame diffusion in the case of a fire accident in a ship or offshore plant. In this study, the sensitivity of the fire-resistance performance and approximation characteristics for the A60 class penetration piece was evaluated by conducting a transient heat-transfer analysis and fire test. The transient heat-transfer analysis was conducted to evaluate the fire-resistance design of the A60 class deck penetration piece, and the analysis results were verified via the fire test. The penetration-piece length, diameter, material type, and insulation density were used as the design factors (DFs), and the output responses were the weight, temperature, cost, and productivity. The quantitative effects of each DF on the output responses were evaluated using the design-of-experiments method. Additionally, an optimum design case was identified to minimize the weight of the A60 class deck penetration piece while satisfying the allowable limits of the output responses. According to the design-of-experiments results, various approximate models, e.g., a Kriging model, the response surface method, and a radial basis function-based neural network (RBFN), were generated. The design-of-experiments results were verified by the approximation results. It was concluded that among the approximate models, the RBFN was able to explore the design space of the A60 class deck penetration piece with the highest accuracy.

Korean Red Ginseng reduces chronic social defeat stress-induced mood disorders via N-methyl-D-aspartate receptor modulation in mice

  • Lee, Bo-Ram;Lee, Ju-Hyun;Ko, Yong-Hyun;Seo, Jee-Yeon;Hur, Kwang-Hyun;Kim, Young-Jung;Kim, Seon-Kyung;Kim, Seong-Eon;Lee, Seok-Yong;Jang, Choon-Gon
    • Journal of Ginseng Research
    • /
    • v.45 no.2
    • /
    • pp.254-263
    • /
    • 2021
  • Background: A chronic social defeat stress (CSDS) model has been proposed as relevant to stress-induced behavioral change in humans. In this study, we examined the effect of Korean Red Ginseng (KRG) on CSDS-induced mood disorders and protein expression in an animal model. Methods: To evaluate the effect of KRG on social defeat stress, test mice were exposed in the resident aggressor's home cage compartment for 14 days beginning 1 h after KRG treatment (10, 20, and 40 mg/kg, per oral (p.o.)). After the exposure, behavioral tests to measure anxiety, social interaction, and depression-like behavior were performed. To investigate the underlying mechanism, N-methyl-D-aspartate receptor expression levels in CSDS-induced mice were evaluated using Western blot analysis. Results: CSDS induced anxiety-like behaviors by decreasing central activity in the open-field test and open-arm approach in the elevated plus maze test and led to social avoidance behavior in the social interaction test. CSDS mice showed upregulated NR1, NR2A, and NR2B expression in the hippocampus. KRG 20 and 40 mg/kg ameliorated anxiety-like activities and KRG 20 mg/kg alleviated social avoidance by decreasing time in the corner zone. KRG treatment recovered CSDS-induced NR1, NR2A, and NR2B protein levels in the hippocampus. Conclusion: These results indicate that KRG has a therapeutic effect on CSDS-induced mood disorder by alleviating N-methyl-D-aspartate receptor overexpression in the hippocampus.

Environmental Fate Tracking of Manure-borne NH3-N in Paddy Field Based on a Fugacity Model (Fugacity 모델에 기초한 논토양에서의 액비살포에 따른 암모니아성 질소 거동추적)

  • Kim, Mi-Sug;Kwak, Dong-Heui
    • Journal of Korean Society on Water Environment
    • /
    • v.35 no.3
    • /
    • pp.224-233
    • /
    • 2019
  • Nitrogen components in liquid manure can reduce safety and quality of environment harmfully. To minimize the environmental risks of manure, understanding fate of manure in environment is necessary. This study aimed at investigating applicability of a simplified Level III fugacity model for simulating $NH_3-N$ component to analyze environmental fate and transport of $NH_3-N$ in liquid manure and to provide basis for improving management of N in the liquid manure system and for minimizing the environmental impacts of N. The model simulation conducted for four environmental compartments (air, water, soil, and rice plants) during rice-cropping to trace $NH_3-N$ component and provided applicability of the Level III fugacity model in studying the environmental fate of $NH_3-N$ in manure. Most of $NH_3-N$ was found in water body and in rice plants depending upon the physicochemical properties and proper removal processes. For more precise model results, the model is needed to modify with the detailed removal processes in each compartment and to collect proper and accurate information for input parameters. Further study should be about simulations of various N-typed fertilizers to compare with the liquid manure based on a modified and relatively simplified Level III fugacity model.

An Assessment of Radiological Consequences of I-131 Atmospheric Release by the System Analysis Method (계통해석법에 의한 I-131대기방출의 영향평가)

  • Yook, Chong-Chul;Lee, Jong-Il;Ha, Chung-Woo
    • Journal of Radiation Protection and Research
    • /
    • v.13 no.1
    • /
    • pp.8-20
    • /
    • 1988
  • The annual individual and collective doses to the thyroids of four age-dependent groups due to the in-take of I-131 released from the Younggwang nuclear power plant NU-1 & 2, Korea, are estimated using the model presented in ICRP 29. Sensitivity and robustness of the model are analyzed. In case of 0.12% fuel defect during normal operation, the collective dose is founded to be 3.05${\times}10^{-3}$man-thyroid-Sv, which is higher than the value calculated by the GASPAR code, 2.3${\times}10^{-3}$man-thyroid-Sv. The maximal individual annual doses resulting from an acute release are higher than those calculated under the assumption of continuous release by $1.4{\sim}1.7$ times. The most important pathway to the infant is milk and, in contrast, that to child, teen and adult is ingestion of crops. The model used is the calculation appears to be influenced by the variables such as roubstness-index. The weighted committed dose equivalent obtained by the ICRP 29 model is slightly higher than that calculated by the three-compartment model.

  • PDF

Assessment of Quantitative Analysis Methods for Lung F-18-Fluorodeoxyglucose PET (폐 종양 FDG PET 영상의 다양한 추적자 역학 분석 방법 개발과 유용성 고찰)

  • Kim, Joon-Young;Choi, Yong;Choi, Joon-Young;Lee, Kyung-Han;Kim, Sang-Eun;Choe, Yearn-Seong;Kim, Yong-Jin;Kim, Byung-Tae
    • The Korean Journal of Nuclear Medicine
    • /
    • v.32 no.4
    • /
    • pp.332-343
    • /
    • 1998
  • Purpose: The purpose of this study was to assess the diagnostic accuracy of various quantitation methods using F-18-fluorodeoxyglucose (FDG) in patients with malignant or benign lung lesion. Materials and Methods: 22 patients (13 malignant including 5 bronchoalverolar cell cancer; 9 benign lesions including 1 hamartoma and 8 active inflammation) were studied after overnight fasting. We performed dynamic PET imaging for 56 min after injection of 370 MBq (10 mCi) of FDG. Standardized uptake values normalized to patient's body weight and plasma glucose concentration (SUVglu) were calculated. The uptake rate constant of FDG and glucose metabolic rate were quantified using Patlak graphical analysis (Kpat and MRpat), three compartment-five parameter model (K5p, MR5p), and six parameter model taking into account heterogeneity of tumor tissue (K6p, MR6p). Areas under receiver operating characteristic curves (ROC) were calculated for each method. Results: There was no significant difference of rate constant or glucose metabolic rate measured by various quantitation methods between malignant and benign lesions. The area under ROC curve were 0.73 for SUVglu, 0.66 for Kpat, 0.77 for MRpat, 0.71 for K5p, 0.73 for MR5p, 0.70 for K6p, and 0.78 for MR6p. No significant difference of area under the ROC curve between these methods was observed except the area between Kpat vs. MRpat (p<0.05). Conclusion: Quantitative methods did not improve diagnostic accuracy in comparison with nonkinetic methods. However, the clinical utility of these methods needs to be evaluated further in patients with low pretest likelihood of active inflammation or bronchoalveolar cell carcinoma.

  • PDF

Surrogate Models and Genetic Algorithm Application to Approximate Optimization of Discrete Design for A60 Class Deck Penetration Piece (A60 급 갑판 관통 관의 이산설계 근사최적화를 위한 대리모델과 유전자 알고리즘 응용)

  • Park, Woo Chang;Song, Chang Yong
    • Journal of the Korean Society of Marine Environment & Safety
    • /
    • v.27 no.2
    • /
    • pp.377-386
    • /
    • 2021
  • The A60 class deck penetration piece is a fire-resistant system installed on a horizontal compartment to prevent flame spreading and protect lives in fire accidents in ships and offshore plants. This study deals with approximate optimization using discrete variables for the fire resistance design of an A60 class deck penetration piece using different surrogate models and a genetic algorithm. Transient heat transfer analysis was performed to evaluate the fire resistance design of the A60 class deck penetration piece. For the approximate optimization of the piece, the length, diameter, material type, and insulation density were applied to discrete design variables, and temperature, productivity, and cost constraints were considered. The approximate optimum design problem based on the surrogate models was formulated such that the discrete design variables were determined by minimizing the weight of the piece subjected to the constraints. The surrogate models used in the approximate optimization were the response surface model, Kriging model, and radial basis function-based neural network. The approximate optimization results were compared with the actual analysis results in terms of approximate accuracy. The radial basis function-based neural network showed the most accurate optimum design results for the fire resistance design of the A60 class deck penetration piece.