• Title/Summary/Keyword: half-dose

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Pharmacokinetics of Recombinant Human Epidermal Growth Factor (DWP401) in Rats (재조합 인간 상피세포성장인자(DWP401)의 흰쥐에서의 약물동태)

  • Chung, Joo-Young;Koh, Yeo-Wook;Nam, Kwon-Ho;Cho, Jae-Youl;Park, Seung-Kook;Yu, Young-Ho;Kim, Jae-Hwan;Han, Kun;Park, Myung-Hwan;Shim, Chang-Koo
    • YAKHAK HOEJI
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    • v.41 no.3
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    • pp.328-334
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    • 1997
  • Pharmacokinetics of DWP401, a recombinant human epidermal growth factor (rhEGF), was studied using radioimmunoassay (RIA) and $^{125}I$-DWP401 in rats. When DWP401 was adm inistered i.v. at doses of 50 and 500 mcg/kg, the plasma DWP401 disappeared biiexponentially with terminal half life of 4.7 and 92.8 min. The $C_{max}$ and $T_{max}$ after s.c. administration of ti at doses of 50 and 500 ${\mu}g$/kg were determined to be 23.6 and 17.5 ng/ml at 50 ${\mu}g$/kg, and 261.4 ng/ml and 36.8 min, respectively. Both the total urinary and biliary recoveries of intact DWP401 2343 very low (<0.4%), probably due to its extensive degradation in the body. the concentration ratio of DWP401 between the organ and plasma decreased especially in the liver and kidney as the dose and time after the dose increased. For example, the liver/plasma and kidney/plasma concentration ratio of DWP401 at 2.5 min after i.v. doses of 50 ${\mu}g$/kg were comparable and much larger than unity. But, the ratio at 2.5 min after i.v. doses of 500${\mu}g$/kg was much larger in the kidney that in than in the liver. These results suggest that the systemic administration of DWP401 might be subject to rapid and extensive clearance from circulation within several hour after main distrbution to liver and kidney.

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Pharmacokinetic Study of YH1885 (I): Absorption, Distribution and Excretion of $^{14)C-YH1885$ in Rats (YH1885의 체내동태(제1보):흰쥐에서 $^{14)C-YH1885$의 단회투여시 흡수, 조직분포 및 배설)

  • Ahn, Byung-Nak;Fujio, Naoki;Kusumoto, Naotoshi;Abe, Yoshifumi;Odomi, Masaaki;Lee, Jong-Wook
    • YAKHAK HOEJI
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    • v.41 no.3
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    • pp.335-344
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    • 1997
  • The absorption, distribution and excretion of $^{14}C$ labeled YH1885 {5,6-Dimethyl-2(4-fluorophenylamino)-4-(1-methyl-1,2,3,4-tetrahydroisoquinolin-2-yl)pyrimidine hydroc hloride), a new proton pumpinhibitor, were investigated in rats after a single administration of $^{14}C$-YH1885. 1. After intravenous administration of 5mg/kg, the blood level of radioactivity declined in a biphasic fashion with the mean terminal elimination half-life of 12.4hr. 2. After oral administration of 20mg/kg, the maximum blood level of radioactirity was reached at 4.0hr in female rats. The blood level of radioactivity-time profiles in male and female rats were similar, and the absorptionof $^{14}C$-YH1885 was not affected by food. 3. Appproximately 89% and 1% of radioactivity of the total dose were excreted in feces and urine, respectively. 4. Biliary excretion of radioactivity was 47.9% of the dose. Enterohepatic circulation of radioactivity was 49.6%. 5. Radioactivity was excreted maily into feces via bile. 6. The concentration of radioactivity in most tissues reached the peak level at 4.0hr after dosing, and then declined. Autoradiograms of male rats showed that the radioactivity levlels in the fat, harder's gland, liver and G-Itract were higher than those in the other tissues and the elimination of radioactivity from fat and liver was slow. 7. Autoradiograms of a pregnant rat showed that radioactivity was transferred to mammary gland, placenta and fetus. The radioactivity level in the mammary gland was higher than that in the blood.

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Sensitivity Analysis for Input Parameters of a Radiological Dose Assessment Model (U. S. NRC Model) for Ingestion Pathways (오염 음식물에 의한 피폭선량 평가모델 (U. S. NRC 모델)의 입력변수에 대한 민감도분석)

  • Hwang, Won-Tae;Suh, Kyung-Suk;Kim, Eun-Han;Choi, Young-Gil;Han, Moon-Hee
    • Journal of Radiation Protection and Research
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    • v.25 no.4
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    • pp.233-239
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    • 2000
  • The sensitivity analysis of input parameters was Performed fer an ingestion dose assessment model (U. S. NRC's Regulatory Guide 1.109 model) from routine releases of radionuclides. In this study, three kinds of typical Korean foodstuffs (rice, leaff vegetables, milk) and two kinds of radionuclides $(^{l37}Cs,\;^{131}I)$ were considered. The values of input parameters were sampled using a Latin hypercube sampling technique based on Monte Carlo approach. Sensitivity indices, which represent the influence or the importance of input parameters for predictive results, were quantitatively expressed by the partial rank correlation coefficients. As the results, the ratio of the interception fraction to the yield of agricultural plants and the human consumption rate were sensitive input parameters for the considered foodstuffs and radionuclides. Additionally, in case of milk, the transfer factor of radionuclides from animal intake to milk and the daily intake rate of feedstuffs were sensitive input parameters. The weathering removal half-life and the delay time from food production to human consumption were relatively sensitive for $^{137}Cs$ and $^{131}I$ depositions, respectively.

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Effects of Hyeolbuchukeo-tang(Xiefuzhuyu-tang) on NO Production in Aortic Vascular Smooth Muscle Cells (혈부축어탕이 대동맥 평활근 세포에서 NO 생성에 미치는 영향)

  • 허재혁;박진영;임준모;장호현;이인;문병순
    • The Journal of Korean Medicine
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    • v.24 no.2
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    • pp.166-178
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    • 2003
  • Objectives : Nitric oxide (NO) plays an important role in normal and pathophysiological cells as a messenger molecule, neurotransmitter, microbiological agent, or dilator of blood vessels and arteriosclerosis, respectively. This study was undertaken to understand the mechanism of NO production and effect of Hyeolbuchukeo-tang (Xiefuzhuyu-tang) on NO production in cultured vascular smooth muscle cell (VSMC). Methods and Results : VSMC was isolated from aorta and cultured. Cultured primary cells were identified as VSMC with anti--smooth muscle actin antibody. A large amount of NO was produced in cultured VSMC treated with $IFN-{\gamma}$ plus TNF in a time- and dose-dependent manner. $TNF-{\alpha}$ was a more efficient stimulator than $IFN-{\gamma}$ in NO production of cultured VSMC. iNOS protein wasdetected within 3 hrs and it increased up to 12 hrs in a time-dependent manner. However, accumulated NO in cytokine-treated VSMC was not detected within 3 hrs. NO production in cytokine-treated VSMC showed the dose- and time-dependent manner, and increased up to 48 hrs. The activated VSMC produced a large amount of NO (about 60 uM). Hyeolbuchukeo-tang (Xiefuzhuyu-tang) alone did not induceNO production, but it potentiated the effect of $TNF-{\alpha}$ on NO production and increased NO production by about 20%. Hyeolbuchukeo-tang (Xiefuzhuyu-tang) did not affect the transcriptional activity of iNOS gene, but increased the accumulation of iNOS. These results indicate that Hyeolbuchukeo-tang (Xiefuzhuyu-tang) could modulate the translational level of iNOS. PKC did not modulate NO production, but calcium ionophore A23187 decreased NO production. However, Hyeolbuchukeo-tang (Xiefuzhuyu-tang) elevated the decreased NO production in A23187-treated VSMC by modulating the stability of iNOS transcripts. Half-life of the synthesized transcripts appeared to have about 6 hrs. PDTC, an $NF-{\kappa}B$ inhibitor, blocked the accumulation of iNOS mRNA, indicating that $NF-{\kappa}B$ served as an important modulator in the transcriptional regulation of iNOS. As Hyeolbuchukeo-tang (Xiefuzhuyu-tang) potentiated the effect of the $TNF-{\alpha}$ on NO production but had no additional effect on PDTC-modulated NO production, it is suggested that Hyeolbuchukeo-tang (Xiefuzhuyu-tang) enhances the $TNF-{\alpha}-mediated$ NO production of VSMC by modulating the iNOS activity and the stability of iNOS transcripts in activated VSMC having the elevated intracellular calcium ion. Conclusions : This study suggests that Hyeolbuchukeo-tang (Xiefuzhuyu-tang) has a potential capacity for preventing and treating diseases of the circulation system, including arteriosclerosis.

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Residual characteristics of Neonicotinoid Insecticide dinotefuran and thiacloprid in cucumber (Neonicotinoide계 농약 dinotefuran과 thiacloprid의 오이 중 잔류특성)

  • Lee, Eun-Young;Noh, Hyun-Ho;Park, Young-Soon;Kang, Kyung-Won;Lee, Kwang-Hun;Park, Hyo-Kyung;Yun, Sang-Soon;Jin, Chung-Woo;Han, Sang-Kuk;Kyung, Kee-Sung
    • The Korean Journal of Pesticide Science
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    • v.13 no.2
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    • pp.98-104
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    • 2009
  • This study was carried out to investigate the residue patterns of two neonicotinoid insecticides, dinotefuran and thiacloprid, commonly used for cucumber, were subjected to indicate a residual characteristic under greenhouse conditions. The pesticides were sprayed onto the crop at recommended and double doses 7 days before harvest and then sampling was done 0, 2, 3, 5, and 7 days after spraying. The amounts of their residues in the crop were analyzed with an HPLC. Their detection limits were 0.01 mg/kg for dinotefuran and 0.005 mg/kg for thiacloprid. Mean recoveries of dinotefuran and thiacloprid were from 85.78 to 89.52 and from 85.71 to 95.31%, respectively. Half-lives of dinotefuran and thiacloprid were 2.8 and 1.8 days at the recommended dose and 2.8 and 1.5 days at the doubled dose, respectively. The ratios of the EDI to ADI by intake the crop harvested 7 days after spraying were less than 0.1% of their ADIs.

Pharmacomkinetics of Roxithromycin after Intravenous Administration in Broilers (록시스로마이신의 정맥주사 후 육계에서의 약물동태학적 분석)

  • Lim Jong-Hwan;Park Byung-Kwon;Kim Myoung-Seok;Hwang Youn-Hwan;Yun Hyo-In
    • Journal of Veterinary Clinics
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    • v.23 no.2
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    • pp.87-90
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    • 2006
  • The aim of the present study was to investigate the disposition pharmacokinetics of roxithromycin in broilers. Roxithromycin was administered at a single dose of 20 mg/kg body weight by intravenous (i.v.) routes. Plasma concentrations of roxithromycin were determined by liquid chromatography/mass spectrometry. After a single i.v. dose plasma concentrations were best fitted to a two-compartment open model. The values of the pharmacokinetic parameters after i.v. administration were: elimination half-life = $5.83{\pm}1.79h$, mean residence time = $6.33{\pm}0.32h$, total body clearance = $0.55{\pm}0.15L/h/kg$, and volume of distribution at steady state = $3.47{\pm}0.84L/kg$. The pharmacokinetic interpretation of roxithromycin after i.v. administration revealed that the drug was well distributed throughout the body in broilers and slowly eliminated. More studies for the application of roxithromycin against poultry disease are needed to establish a suitable pharmaceutical formulation, propose optimum dosage regimens, investigate clinical efficacy and study the tolerability of repeated doses.

Serum Concentration and Exposure History of Dioxins and Organochlorine Pesticides among Residents around the Camp Carroll Area (캠프캐럴 인근 주민에서 다이옥신류 및 유기염소계 농약의 혈중 농도 및 노출력)

  • Bae, Sang Geun;Kim, Geun-Bae;Cho, Yong-Sung;Lee, Yu-mi;Lee, Duk Hee;Yang, Wonho;Ju, Young-Su;Lee, Kwan;Min, Young-Sun;Lim, Hyun-Sul
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.26 no.3
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    • pp.277-285
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    • 2016
  • Objectives: This study was performed in order to evaluate whether 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) could be detected among residents living near Camp Caroll in Waegwan and whether serum concentrations of dioxins, including 2,3,7,8-TCDD, and organochlorine pesticides (OCPs) are associated with length of residence. Methods: Study subjects totaled 113 (for dioxins) and 190 (for OCPs) adults who were selected from participants in a medical investigation. Serum concentrations of dioxins and OCPs were measured using HRGC/HRMS. Information on length of residence was obtained through questionnaires. Results: 2,3,7,8-TCDD was not detected in serum among all subjects. When length of residence was classified as a categorical variable, after adjusting for confounding variables, only residents living in Waegwan for 40 years or longer tended to have high total TEQ values and 2,3,4,7,8-PeCDF with marginal significances. There was no dose-response relation between length of residence and serum concentrations of these chemicals. In multiple regression models with continuous values of the length of residence, total TEQ value and 1,2,3,4,6,7,8-HpCDF were positively associated with length of residence. However, they explained about 3-5% of total variations of serum concentrations of these compounds, while age, consumption of fatty fish, body mass index, alcohol drinking, and cigarette smoking were main variables affecting serum concentrations of dioxins or OCPs. Conclusions: In the current study, high concentrations of certain compounds were mainly observed among persons who lived in Waegwan for at least for 40 years without a dose-response relation. Therefore, it seems difficult to conclude that length of residence meaningfully contributed to the current serum concentrations of dioxins or OCPs among residents in Waegwan. However, considering the half-life of 2,3,7,8-TCDD and indirect exposure routes, the limitations of the current study design should be considered in the interpretation of the study findings.

Conceptual Source Design and Dosimetric Feasibility Study for Intravascular Treatment: A Proposal for Intensity Modulated Brachytherapy (혈관내 방사선치료를 위한 이론적 선원 설계 및 선량적 관점에서의 적합성 연구: 출력변조를 이용한 근접치료에 대한 제안)

  • Kim Siyong;Han Eunyoung;Palta Jatinder R.;Ha Sung W.
    • Radiation Oncology Journal
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    • v.21 no.2
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    • pp.158-166
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    • 2003
  • Purpose: To propose a conceptual design of a novel source for intensity modulated brachytherapy. Materials and Methods: The source design incorporates both radioactive and shielding materials (stainless steel or tungsten), to provide an asymmetric dose intensity in the azimuthal direction. The intensity modulated intravascular brachytherapy was performed by combining a series of dwell positions and times, distributed along the azimuthal coordinates. Two simple designs for the beta-emitting sources, with similar physical dimensions to a $^{90}Sr/Y$ Novoste Beat-Cath source, were considered in the dosimetric feasibility study. In the first design, the radioactive and materials each occupy half of the cylinder and in the second, the radioactive material occupies only a quater of the cylinder. The radial and azimuthal dose distributions around each source were calculated using the MCNP Monte Carlo code. Results: The preliminary hypothetical simulation and optimization results demonstrated the 87$\%$ difference between the maximum and minimum doses to the lumen wall, due to off-centering of the radiation source, could be reduced to less than 7$\%$ by optimizing the azimuthal dwell positions and times of the partially shielded intravascular brachytherapy sources. Conclusion: The novel brachytherapy source design, and conceptual source delivery system, proposed in this study show promising dosimetric characteristics for the realization of intensity modulated brachytherapy in intravascular treatment. Further development of this concept will center on building a delivery system that can precisely control the angular motion of a radiation source in a small-diameter catheter.

Effects of Morphine and Buprenorphine Intravenous Infusion for Postoperative Pain (Morphine과 Buprenorphine의 지속적 정주에 의한 술후 통증 억제효과의 비교)

  • Baek, Sun-Ki;So, Sang-Yoon;Han, Young-Jin;Choe, Huhn
    • The Korean Journal of Pain
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    • v.7 no.1
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    • pp.78-83
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    • 1994
  • Morphine, a $\mu$-receptor agonist, produces strong analgesic effect with some side effects such as nausea, vomiting, urinary retension, somnolence, and respiratory depression. Buprenorphine also provides strong analgesic effects, and hemodynamic changes after continuous infusion of morphine, or buprenorphine-ketorolac combination in gynecologic patients. Analgesic effect was assessed by visual analogue scale(VAS) and Prince Henry scale(PHS). Morphine group, initial 2 mg of bolus morphine was followed by 48 mg/96 ml of continuous infusion. Buprenorphine group, initial 0.1 mg of buprenorphine was followed up with infusion by 2.3 mg/100 ml. Half dose of both initial bolus and maintenance buprenorphine with ketorolac 15 mg for bolus and 60 mg for maintenance were infused in buprenorphine-ketorolac combination group. No significant hemodynamic changes were seen in any of the groups. VAS significantly decreased after 15 minutes of infusion in all three groups, and was significantly lower in morphine group than the other 2 groups, after 60 minutes. PHS was decreased significantly 15 minutes after infusion in the morphine group, and after 60 minutes in two other groups. The incidence of side effects were similar between morphine and buprenorphine groups, but significantly reduced in buprenorphine-ketorolac combination group. We concluded that buprenorphine could be an alternative to morphine for postoperative pain, and smaller dose of buprenorphine could be used if it is combined with ketorolac with less side effects.

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Comparative Study on the Committed Dose Equivalent for Adults and Infants (예탁선양치(預託線量値)에서 본 성인(成人)과 유아(幼兒)와의 비교연구(比較硏究))

  • Sung, Kye-Yong;Yook, Chong-Chul;Ha, Chung-Woo
    • Journal of Radiation Protection and Research
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    • v.9 no.2
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    • pp.76-89
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    • 1984
  • Weighted committed dose equivalents($W_T\;H_{50}$) per intake of unit activity of four nuclides-I-131, I-133, Cs-134 and Cs-137-, which was based on the concepts of ICRP Pub. 30, are calculated for adult who is 70 kg and 25 years old and, for infant who is 10 kg and 1 year old. Metabolism of iodine taken through oral or inhalation pathway is described by using the three-compartment model which consists of inorganic, thyroid and organic compartment. After intake, the amount of iodine in every compartment is calculated by solving the transfer equations among the these compartments. As soon as caesium is taken into the body, it is distributed uniformly in the body through the transfer compartment. In this case, the amount of caesium in total body is calculated by using the total body compartment model which is divided into two tissue compartments because of their different biological half-lifes of caesium in body. As a result of calculations, whether oral or inhalation pathway, the values of ($W_T\;H_{50}$) per intake of unit activity of I-131 for infants are about ten times as much as those of adults. On the other hand, for Cs-134 and Cs-137, the values of $W_T\;H_{50}$ per intake of unit activity show that, whether adults of infants, they have almost the same values.

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