• Biomolecules & Therapeutics
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• 제6권4호
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• pp.400-405
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• 1998

The pharmacokinetics of CJ-50001 (recombinant human granulocyte-colony stimulating factor, developed by R&D center of Cheil Jedang Corp.) were investigated in rats and dogs. The serum concentrations of CJ-50001 were measured by a sandwich enzyme immunoassay. After single intravenous (iv) administration of Cf-50001 to rats at a dose of 5 $\mu$g/kg, the mean terminal half-life and area under the concentration-time curve (AUC) were 0.96 h and 124.497g . h/ml, respectively. After single subcutaneous (sc) administration at the same dose, maximum serum concentration was observed at about 2 hours after administration, and the mean terminal half-life, AUC and the bioavailability were 1.11 h,63.58$\mu$g . h/ml and 51.07%, respectively. In repeated dosing studies, CJ-50001 was administered iv and sc to rats at a daily dose of 5$\mu$g/kg for 7 days. The pharmacokinetic parameters, such as mean AUC and terminal half-life, were no significantly different from those of single administration. Following single iv and sc administration of CJ-50001 to dogs at a dose of 5 $\mu$g/kg, mean AUCs were much higher than those of rats, due to the decreased clearence (CL). After sc administration to dogs, maximum serum concentration was observed at 2~4 hours after administration and the bioavailability was 54.60%.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 춘계학술대회
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• pp.3-5
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• 1997

Properties of a good drug include safety, efficacy, half-life and bioavailability. With the current approach to drug discovery based on receptor-based and cell-based screening methods, compounds are frequently moved into development with poor bioavailability. With low bioavailability, drug administration is typically limited to parenteral routes, thus limiting the potential wide-spread utility of these therapeutic agents. The first and most important factor limiting a drug's bioavailability is the intestinal membrane permeability which in turn determines the maximum fi:action of the dose administered that can be absorbed. We have recently utilized new intubation methods for performing permeability measurements in humans and establishing a fundamental human data base for correlating intestinal jejunal membrane permeabilities with permeabilities determined in other systems, e.g., animals, tissue culture, as well as physical chemical properties.

• Archives of Pharmacal Research
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• 제24권6호
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• pp.584-589
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• 2001

Isopropryl 2-(1-3-dithiethane-2-ylidene)-2 [N-(4-methyl-thiazole-2-yl) carbamoyl] acetate (YH439) is currently under phase ll clinical trials by the Yuhan Research Center for use as a hepatoprotective agent. Unfortunately, the oral bioavailbility of YH439, which is sparingly soluble in water (i.e., $0.3{\;}\mu\textrm{g}/ml{\;}or{\;}0.91{$\mu}M$ at room temperature), reportedly, is negligibleregardless of the dose administered to rats in the 10-300 mg/kg range. The bioavailability of the compound increased up to 24%, when administered in the form of a micellar solution ($700{\;}\mu\textrm{g}/ml$or 2.1 mM for YH439) at a dose of 10 mg/kg, suggesting that its limited solubility is associated with its negligible bioavailability. In order to obtain additional informmation concerning the bioavailability of YH439, the mechanism(s) involved in gastrointestinal (Gl) absorption were investigated in the present study. For this purpose, the transport of YH430 across a Caco-2 cell monolayer was measured in a $Transwell^{\circledR}$. A permeability of $4.07{\times}10^{-5}{\;}cm/s$ was obtained for the absorptive (i.e., apical to basolateral direction) transport of $0.42{\mu}M$ YH439, implicating that the in vivo Cl absorption is nearly complete. The absorptive transport exhibited a slight concentration-dependency with an intrinsic clearance ($CL_{i}$) of $0.38{\mu}L/{\textrm{cm}^2}/sec$, which accounted for 28.1% of the total intrinsic clearance (i.e., $CL_i$ plus the intrinsic clearance for the linear component) of the transport. Thus, saturation of the absorption process appears to be a minor factor in limiting the bioavailability of the compound. The apparent permeability of YH439 from the basolateral to the apical direction (i.e., efflux, $6.67{\times}10^{-5}{\;}cm/s$) was comparable to that for absorptive transport, but, interestingly, a more distinct concentration-dependency was observed for this transport. However, the efflux does not appear to influence the bioavailability of the compound, as evidenced by the sufficiently high permeability in the absorption direction. Rather, a reportedly extensive first-pass hepatic metabolism appears to be a principal factor in limiting the bioavailability. In this respect, reducing the first-pass metabolism by some means would lead to a higher bioavailability of the compound. Thus, elevation of the absorption rate of YH439 becomes a necessity. From a practical point of view, increasing the concentration of YH439 in the Cl fluid appears to be a feasible way to increase the absorption rate, because the compound is primarily absorbed via a linear mechanism. In summary, the solubilization of YH439, as previously demonstrated for a micellar solution of the compound, appears to be a practical way to increase the oral bioavailability of YH439.

• Environmental Engineering Research
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• 제18권3호
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• pp.177-189
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• 2013

Studies were carried out on the speciation of heavy metals (Zn, Cu, Mn, Fe, Ni, Pb, Cd, and Cr) during rotary drum composting of water hyacinth (Eichhornia crassipes) for a period of 20 days. Five different proportions of cattle manure, water hyacinth and sawdust were prepared for composting. This study concluded that, rotary drum was very efficient for the degradation of organic matter as well as for the reduction of mobility and bioavailability of heavy metals during water hyacinth composting. The results from the sequential extraction procedure of heavy metals shows that rotary drum composting changed the distribution of five fractions of Zn, Cu, Mn, Fe, Ni, Pb, Cd, and Cr. The highest reduction in the bioavailability factors of Pb and Cd was observed during the process. The total concentration of Cu, Cr, and Cd was very low compared to the other metals (Zn, Mn, Fe, Ni, and Pb); however, the percentage of exchangeable and carbonate fractions of these metals was similar to other metals. These results confirmed that the bioavailability of metals does not depend on the total concentration of metals. From this study, it can be concluded that the addition of an appropriate proportion of cattle manure significantly reduced the mobile and easily available fractions (exchangeable and carbonate fractions) during water hyacinth composting in rotary drum.

• 약학회지
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• 제42권5호
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• pp.513-518
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• 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.

• 한국환경과학회지
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• 제26권7호
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• pp.847-858
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• 2017

For 26 soil series distributed more than 1% among 63 soil series in Jeju Island, natural uncultivated soil samples were collected. For these soils, the chemical speciation of eight heavy metals (Cd, Cr, Cu, Mn, Ni, Pb, V, and Zn) was examined. Further, the Plant Bioavailability (PB) and Mobility Factor (MF) of these heavy metals were evaluated using Tessier's 5-step sequential extraction method (exchangeable, carbonate, reducible (bound to Fe/Mn oxides), oxidizable (bound to organic matter), and residual fraction). The main form present was residual fraction for Cd and Zn; residual and oxidizable fractions for Cr, Cu, Ni, and Pb; reducible fraction for Mn; and carbonate fraction for V. The average plant availability and average mobility factor were found to be V (57.37%) > Zn (12.49%) > Cd (11.76%) > Cu (11.19%) > Pb (9.37%) > Cr (9.09%) > Mn (3.13%) > Ni (2.63%), and Mn (61.04%) > V (59.94%) > Zn (31.54%) > Cd (17.65%) > Cr (15.66%) > Ni (13.89%) > Pb (13.80%) > Cu (13.53%), respectively.

• Applied Microscopy
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• 제47권3호
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• pp.148-156
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• 2017

The wide distribution of redox-sensitive elements (RSE) as arsenic (As), cadmium (Cd), selenium (Se), and strontium (Sr) in the top soil of Siwaqa area are related to the weathering action of alkaline surface and groundwater on the parent rocks. The bioavailability, distribution, sorption, and ecotoxicity of As, Cd, Se, and Sr, of the wild plants and top soils in the study area were investigated. A total number of 23 surface soil samples and 23 plant samples were collected and analyzed for the most toxic elements. The uptake of elements by plants was dependent on the plant species and the concentration of elements in the soil. For example, Sr was the highest concentration in soil samples and plants, while Se was the lowest concentration in soil samples and pants. For the plants, the results showed that Bellevalia sp. had the highest elements uptake, while Allium rothii had the lowest elements uptake. The results of this work provide a valuable knowledge for understanding the bioavailability of some toxic elements in the soil and plants of Central Jordan. The results are expected to be of great help for the Jordanian Uranium Mining Company during their environmental risk assessments.

• Environmental Engineering Research
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• 제20권3호
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• pp.212-222
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• 2015

Experiments were conducted on the immobilization of eight heavy metals (HMs) (Zn, Cu, Mn, Fe, Ni, Pb, Cd, and Cr) during 20-day rotary drum composting of water hyacinth. The Tessier sequential extraction procedure was used to investigate the fractionation of HMs. The eco-toxicity risk of HMs was assessed by risk assessment code (RAC). In the results, the bioavailability factor (BAF) for different HMs presented in the following order: Mn > Zn = Fe > Cu > Cr > Cd = Pb > Ni. The total concentration of Pb was higher than that of Zn, Cu, Mn, Cd and Cr; however, its BAF was the lowest among these HMs. These results confirmed that the eco-toxicity of HMs depends on bioavailable fractions rather than on the total concentration. The greatest reduction in bioavailability and eco-toxicity risk of HMs occurred in lime 1% and 2% as compared to control and lime 3%. The eco-toxicity risk of Fe, Ni, Pb, Cd and Cr was reduced from low risk to zero risk by rotary drum composting. These studies demonstrated the high efficiency of the rotary drum for degrading compost materials and for reducing the bioavailability and eco-toxicity risk of HMs during the composting process.

• 한국식품위생안전성학회지
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• 제7권4호
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• pp.165-172
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• 1992

Among the nutrients of biological importance, minerals are of particular interest in human nutrition because the range of adequate intake is so narrow. As the results of a series of interaction experiments between dietary fiber sources and minerals, there are many inconsistencies in the experimental data regarding the effect of dietary fibers on mineral bioavailability. the mechanism by which dietary fiber might influence mineral absorption is related to its physicochemical properties. These properties involve the ability of dietary fiber to (1) act as a weak cation exchanger, (2) decrease transit time, (3) dilute mineral concentration by increasing fecal bulk and (4) resist digestion in the large bowel. Regardless of the large number of human and animal studies available, a carful review of these publications dose not provide the answer as to whether the adverse effect of dietary fibers on mineral absorption is the fiber itself or some associated dietary factors( e.g. phytate, oxalate, ascorbate, citrate and protein, mineral-mineral interaction, etc) that are responsible for this action. As a result of the complexity of interaction that may take place between minerals. dietary fiber, and other component of food ; it becomes very difficult to blame fiber alone as a negative factor of mineral nutrition. We absolutely need more research with advanced tools rather than metabolic balance study.

• Environmental Analysis Health and Toxicology
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• 제27권
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• pp.5.1-5.10
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• 2012

Objectives: The purpose of this study was to assess the risk of ingestion exposure of lead by particle sizes of crumb rubber in artificial turf filling material with consideration of bioavailability. Methods: This study estimated the ingestion exposure by particle sizes (more than 250 um or less than 250 um) focusing on recyclable ethylene propylene diene monomer crumb rubber being used as artificial turf filling. Analysis on crumb rubber was conducted using body ingestion exposure estimate method in which total content test method, acid extraction method and digestion extraction method are reflected. Bioavailability which is a calibrating factor was reflected in ingestion exposure estimate method and applied in exposure assessment and risk assessment. Two methods using acid extraction and digestion extraction concentration were compared and evaluated. Results: As a result of the ingestion exposure of crumb rubber material, the average lead exposure amount to the digestion extraction result among crumb rubber was calculated to be $1.56{\times}10^{-4}$ mg/kg-day for low grade elementary school students and $4.87{\times}10^{-5}$ mg/kg-day for middle and high school students in 250 um or less particle size, and that to the acid extraction result was higher than the digestion extraction result. Results of digestion extraction and acid extraction showed that the hazard quotient was estimated by about over 2 times more in particle size of lower than 250 um than in higher than 250 um. There was a case of an elementary school student in which the hazard quotient exceeded 0.1. Conclusions: Results of this study confirm that the exposure of lead ingestion and risk level increases as the particle size of crumb rubber gets smaller.