• Title/Summary/Keyword: Dose-dependency

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Implication of ICRP pediatric reference voxel phantoms on dose assessment of patients in radioiodine therapy

  • Soo Min Lee;Chansoo Choi;Ji Won Choi;Chul Hee Min;Seulki Ko;Bangho Shin;Chan Hyeong Kim;Yeon Soo Yeom
    • Nuclear Engineering and Technology
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    • v.56 no.6
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    • pp.2247-2257
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    • 2024
  • To investigate the impact of the recently released pediatric reference voxel phantoms (0-, 1-, 5-, 10-, 15-year-old males and females) of the International Commission on Radiological Protection (ICRP) on organ dose estimates for radioactive iodine (RAI) treatment in pediatric patients, we calculated and analyzed pediatric-specific iodine131 S values (rT ← thyroid) for the 30 radiosensitive organs by conducting Monte Carlo simulations using the Geant4. The gender dependency in the S values was frequently seen for the 15-year-old phantoms with higher S values of female than male. In addition, the age dependency in the S values was observed for most target organs; that is, the S values tend to decrease for older ages (e.g., ~120 times for the gonads between the adult and newborn) due mainly to the inter-organ distances generally longer for older ages. Moreover, we observed that the iodine-131 S values tend to be significantly greater by up to ~145.5 times than those of the stylized phantoms that have been widely used for organ dose estimates of pediatric RAI patients. We believe that the pediatric-specific iodine-131 S values (rT ← thyroid) of the ICRP pediatric reference voxel phantoms should be beneficial to improve the dosimetry of pediatric RAI patients.

Bioavailabilities of Omeprazole Administered to Rats through Various Routes

  • Choi, Mi-Sook;Lee, Young-Hee;Shim, Chang-Koo
    • Archives of Pharmacal Research
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    • v.18 no.3
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    • pp.141-145
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    • 1995
  • Omeprazole, a proton pump inhibitor, was given intravenously (iv), orally (po), intraperitoneally (ip), hepatoportalvenously (pv), and intrarectally (ir) to rats at a dose of 72mg/kg in order to investigate the bioavailability of the drug, The extent of bioavailabilities of omeprazole administered through pv, ip, po, and ir routes were 88.5, 79.4, 40,8, and 38.7%, respectively. Pharmacokinetic analysis in this study and literatures (Regardh et al., 1985 : Watanabe et al., 1994) implied significant dose-dependency in hepatic first-pass metabolism, clearance and distribution, and acidic degradation in gastric fluid. The high bioavailability from the pv administration (88.5%) means that only 11.5% of dose was extracted by the first-pass metabolism through the liver at this dose (72 mg/kg). The low bioavailability from the oral administration (40.8%) in spite of minor hepatic first-pass extraction indicates low transport of the drug from GI lumen to portal vein. From the literature (Pilbrant and Cederberg, 1985), acidic degradation in gastric fluid was considered to be the major cause of the low transport. Thus, enteric coating of oral preparations would enhance the oral bioavailability substantially. The bioavailability of the drug from the rectal route, in which acidic degradation and hepatic first-pass metabolism may not occur, was low (38.7%) but comparable to that from the oral route (40.8 %) indicating poor transport across the rectal membrane. In this case, addition of an appropriate absorption enhancer would improve the bioavailability. Rectal route seems to be an possible alternative to the conventional oral route for omeprazole administration.

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Pharmacokinetics of Recombinant Human Granulocyte Colony Stimulating Factor (rhG-CSF) Following Intravenous, Intramuscular and Subcutaneous Administration of HM10411 and Filgrastim to Rats and Mice (인과립구 콜로니 자극인자 제제인 HM10411와 필그라스팀의 정맥, 근육 및 피하 주사시 흰쥐와 마우스에서의 약물 동태)

  • Kim, In-Wha;Lee, Sang-Hoon;Kim, Young-Min;Jung, Sung-Youb;Kwon, Se-Chang;Lee, Gwan-Sun;Chung, Suk-Jae;Shim, Chang-Koo
    • Journal of Pharmaceutical Investigation
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    • v.31 no.2
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    • pp.89-94
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    • 2001
  • The pharmacokinetics of recombinant human granulocyte colony stimulating factor (rhG-CSF) following intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administration of HM1041l-lyo and HM10411-liq (lyophilized and liquid formulations of rhG-CSF, recently under development by Hanmi Pharmaceutical Company) were studied in rats, and compared with that of Filgrastim (conventional formulation of rhG-CSF on market). The plasma concentration of rhG-CSF was quantified using a specific ELISA. The pharmacokinetic parameters of rhG-CSF, after i.v., i.m. and s.c. administration of Filgrastim, HM1041l-lyo and HM1041l-liq to rats at a rhG-CSF dose of $10\;{\mu}g/kg$, were almost identical among the three formulations. No dose-dependency was observed in the pharmacokinetic parameters of rhG-CSF following i.v. administration in the dose range of $5{\sim}100\;{\mu}g/kg$. rhG-CSF, after i.v. administration of the three preparations at a dose of $10\;{\mu}g/kg$ to rats, was detected at low levels in all of the body tissues with highest tissue/plasma ratio of $0.46{\sim}0.51$ for the kidney at 30 min after the administration. The pharmacokinetics of rhG-CSF, after i.v. administration to mice at a dose of $10\;{\mu}g/kg$, were comparable among the three formulations. In conclusion, HM10411-lyo and HM10411-liq exhibited similar pharmacokinetics for rhG-CSF with Filgrastim regandless of animal species. Considering the fact that HM10411 series, contrary to Filgrastim, are proteins lacking a methionine residue, the methionine moiety in rhG-CSF molecule does not appear to influence the pharmacokinetics of the protein significantly.

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The Comparison of Absolute Dose due to Differences of Measurement Condition and Calibration Protocols for Photon Beams (6MV 광자선에서 측정조건의 변화와 측정법의 차이에 의한 절대 선량값의 비교)

  • Kim, Hoi-Nam
    • The Journal of Korean Society for Radiation Therapy
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    • v.10 no.1
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    • pp.11-22
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    • 1998
  • The absolute absorbed dose can be determined according to the measurement conditions ; measurement material, detector, energy and calibration protocols. The purpose of this study is to compare the absolute absorbed dose due to the differences of measurement condition and calibration protocols for photon beams. Dosimetric measurements were performed with a farmer type PTW and NEL ionization chambers in water, solid water, and polystyrene phantoms using 6MV photon beams from Siemens linear accelerator. Measurements were made along the central axis of $10{\times}10cm$ field size for constant target to surface distance of 100cm for water, solid water and polystyrene phantom. Theoretical absorbed dose intercomparisons between TG21 and IAEA protocol were performed for various measurement combinations on phantom, ion chamber, and electrometer. There were no significant differences of absorbed dose value between TG2l and IAEA protocol. The differences between two protocols are within $1\%\;while\;the\;average\;value\;of\;IAEA\;protocol\;was\;0.5\%$ smaller than TG2l protocol. For the purpose of comparison, all the relative absorbed dose were nomalized to NEL ion chamber with Keithley electrometer and water phantom, The average differences are within $1\%,\;but\;individual\;discrepancies\;are\;in\;the\;range\;of\;-2.5\%\;to\;1.2\%$ depending upon the choice of measurement combination. The largest discrepancy of $-25\%$ was observed when NEL ion chamber with Keithley electrometer is used in solid water phantom. The main cause for this discrepancy is due to the use of same parameters of stopping power, absorption coefficient, etc. as used in water phantom. It should be mentioned that the solid water phantom is not recommended for absolute dose calibration as the alternative of water, since absorbed dose show some dependency on phantom material other than water. In conclusion, the trend of variation was not much dependent on calibration protocol. However, It shows that absorbed dose could be affected by phantom material other than water.

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The Effect of a Single Administration of rG-CSF on the Peripheral Neutrophil Levels and Its Dose Responsiveness in Normal ICR mice and SD rats (정상 ICR mouse 및 SD rat에서 CJ-50001 (rG-CSF)의 단회투여후 말초호중구수의 변동 및 용량상관성)

  • 임동문;조효진;김달현;이현수;김제학;김현수
    • Biomolecules & Therapeutics
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    • v.5 no.4
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    • pp.380-383
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    • 1997
  • CJ-50001 is a recombinant granulocyte-colony stimulating factor (rG-CSF) developed by Cheil Jedang R&D Center. The effects of CJ-50001 on the increase of peripheral neutrophil count following intravenous and subcutaneous single administration at a dose of 20$\mu$g/kg in normal ICR mice and SD rats, respectively, were compared with those of Grasin, a control drug. Both CJ-50001 and Grasin significantly increased the peripheral neutrophil number in four treatment groups and the maximum number of neutrophil was achieved at 12 to 18 h in rats and mice, respectively. The dose dependency test was studied for CJ-50001 only in normal mice by intravenous or subcutaneous administration. When administered i.v or s.c at the various doses in normal mice, CJ-50001 significantly increased the neutrophil number over the dose of 160 ng/kg, compared with the vehicle control group. From these results, it was concluded that CJ-50001 showed efficacy similar to Grasin in the peripheral neutrophil count increase.

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Dose Dependency of Earthworm Powder on Antithrombotic and Fibrinolytic Effects

  • Kim, Yeong-Shik;Pyo, Mi-Kyung;Park, Kyung-Mi;Hahn, Bum-Soo;Yang, Kyung-Youl;Choi, Hye-Sook Yun
    • Archives of Pharmacal Research
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    • v.21 no.4
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    • pp.374-377
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    • 1998
  • The freeze-dried powder of Lumbricus rubellus earthworm was administered orally to rats and its fibrinolytic and antithrombotic effects were investigated. The fibrinolytic activity of plasma was determined by measuring the plasmin activity of the euglobulin fraction and was increased to two-folds of the control at a dose of 0.5 g/kg/day and five times with 1 g/kg/day after 4-day administration. The antithrombotic effect was studied in an arterio-venous shunt model of rats. The thrombus weight decreased significantly from 43.2 mg to 32.4 mg at a dose of 0.5 g/kg/day after 8-day treatment. The level of fibrinogen/fibrin degradation product (FDP) in serum was elevated in a dose-dependent manner during the treatment period. On the 8th day after administration, the FDP value was increased to 7.7 $\mu\textrm{g}$g/ml compared with the control value of 3.3 $\mu\textrm{g}$g/ml. These results support that earthworm powder is valuable for the prevention and/or treatment of thrombotic conditions.

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Effect of Phenobarbital on the Nonlinear Pharmacokinetics of Naproxen (나프록센의 비선형 체내동태에 미치는 페노바르비탈의 영향)

  • Lee, Yong-Bok;Chae, Myung-Ae;Koh, Ik-Bae
    • Journal of Pharmaceutical Investigation
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    • v.27 no.2
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    • pp.109-117
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    • 1997
  • In order to elucidate the effect of phenobarbital (PB) on the nonlinear pharmacokinetic behavior of naproxen (NAP), we compared the dose dependent hepatic intrinsic clearance, biliary excretion and protein binding of NAP in control rats to those in the PB-pretreated rats which were intraperitoneally pretreated with PB sodium (75 mg/kg) once a day for four days. NAP was injected via femoral (1.5 mg/kg) and portal(0.25, 0.5, 1.5, 15 and 30 mg/kg) vein to the control and PB-pretreated rats, respectively. And also, we measured the plasma free fraction of NAP with the equilibrium dialysis method and the biliary excreted total amounts of NAP in both rats. Plasma free fraction of NAP was decreased in lower concentration than $150\;{\mu}g/ml$ of NAP due to PB pretreatment. In higher concentration, however, plasma free fraction was increased. These in vitro results suggest that the total protein concentration was increased but the total binding capacity of NAP to protein was decreased by PB-pretreatment. The total plasma clearance and the hepatic intrinsic clearance of NAP had similar values in both groups, respectively. And, both clearances of NAP were significantly increased by PB-pretreatment. Even though the plasma free fractions of NAP in both groups were constantly remained within the concentration range according to the increase of administration dose, the hepatic intrinsic clearances of NAP were significantly increased in both groups with the increased dose. And, the biliary excreted total amounts of NAP were significantly increased by PB-pretreatment at the lower dose, but decreased at the higher dose. These in vivo results suggest that NAP represents the uncommon nonlinear pharmacokinetic behavior that the hepatic intrinsic clearance was enhanced with the increased dose, and that PB enhances further the hepatic intrinsic clearance of NAP with the increased dose due to its enzyme induction effect.

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Study on the Dose Characteristics of the PTW-LinaCheck Dosimeter and Its Application to Daily Output Measurement (PTW-LinaCheck 측정기의 선량 특성과 일일 출력측정 응용에 관한 연구)

  • Jeong, Dong-Hyeok;Lee, Kang-Kyoo;Moon, Un-Chul;Kim, Hyun-Jin;Kim, Young-Seok;Moon, Sun-Rock
    • Progress in Medical Physics
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    • v.19 no.1
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    • pp.56-62
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    • 2008
  • In this study, we have investigated the dose characteristics of PTW-LinaCheck designed to detect output of medical LINAC and discussed clinical use of the detector. The reproducibility, linearity, and dose rate dependency of the dosimeter were measured for photons of 6 and 15MV and the electrons of 4, 6, 9, 12, and 16MeV. To know the error ranges of the measured data in daily output measurement, the response variations due to geometrical setup errors were measured. As a result of measurement, the error range from the geometrical setup and the reproducibility was less than ${\pm}0.6%$ for given beam qualities in daily output measurement, where the errors from the linearity and the dose rate dependency were negligible. Finally, we concluded that the LinaCheck dosimeter has a good characteristics in terms of dose and setup convenience in daily output measurement. In addition we have shown an examples of clinical use of this dosimeter for measuring daily output more than 60 days.

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Sensitivity Variations with pre-irradiation dose to P-type Semi conductor for radiation dosimetry

  • 최태진;김옥배
    • Progress in Medical Physics
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    • v.6 no.1
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    • pp.49-57
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    • 1995
  • The semiconductor detector has a high sensitive to radiation and a small volume. It has been frequently used in high energy photon and electron beamdosimetry. However, Semiconductor detector are subject to radiation damage in high energy radiation beam which reduces the sensitivity and creat a large discrepancy. In this experiments, P-type semiconductor was irradiated to 18 MeV electron beam with pre-irradiation for reducing the sensitivity for high reproducibility and investigated the dose characteristics against the dose rate variations. The sensitivity per unit dose in small dose rate showed a 35% large different to a large dose rate with pre-irradiation dose for 0.5 KGy and 20% for 3 KGyin this study. The silicon detector has showed a large dependency of beam direction with 13% discrepancy and a linear sensitive as increased temperature.

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Effect of Inositol-phosphatase on Fc Receptor-mediated Phagocytosis of Macrophages (대식세포의 Fc 수용체를 통한 탐식에 미치는 Inositol-phosphatase의 영향)

  • Kim, Jong-Hyun
    • IMMUNE NETWORK
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    • v.5 no.3
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    • pp.144-149
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    • 2005
  • Background: Fc receptor-mediated phagocytosis is a complex process involving the activation of kinases and phosphatases. FcgammaRIIB has been known to transduces inhibitory signals through an immunoreceptor tyrosine-based inhibitory motif (ITIM) in cytoplasmic domains. In this study, we examined the involvement of inositol-phosphatase in the Fc receptor-mediated phagocytosis. Methods: J774 cells were infected using vaccinia viral vector containing SH2 domain-containing inositol-phosphatase (SHIP) cDNA and stimulated with the sensitized sheep red blood cells. Results: Stimulation of J774 cells induced the tyrosine phosphorylation of SHIP which was maximal at 5 minutes. Phosphatidylinositol-3 (PI-3) kinase inhibitor (wortmannin) inhibits J774 cell phagocytosis of sensitized sheep red blood cells in a dose-dependent manner. Heterologious expression of SHIP in J774 cells inhibits phagocytosis of sensitized sheep red blood cells in a dose-dependency manner, but catalytically dead mutants of SHIP has no effect on phagocytosis. Conclusion: These results strongly suggest that the active signals mediated by PI-3 kinase are opposed by inhibitory signals through SHIP in the regulation of Fc receptor-mediated phagocytosis.