• 한국임상약학회지
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• 제26권2호
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• pp.150-162
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• 2016

Objective: First-in-human dose estimation is an essential approach for successful clinical trials for drug development. In this study, we systematically compared first-in-human dose and human pharmacokinetic parameter estimation approaches. Methods: First-in-human dose estimation approaches divided into similar drug comparison approaches, regulatory guidance based approaches, and pharmacokinetic based approaches. Human clearance, volume of distribution and bioavailability were classified for human pharmacokinetic parameter estimation approaches. Results: Similar drug comparison approaches is simple and appropriate me-too drug. Regulatory guidance based approaches is recommended from US Food and Drug Administration (FDA) and European Medicines Agency (EMA) regarding no-observed-adverse-effect level (NOAEL) or minimum anticipated biological effect level (MABEL). Pharmacokinetic based approaches are 8 approaches for human clearance estimation, 5 approaches for human volume of distribution, and 4 approaches for human bioavailability. Conclusion: This study introduced and compared all methods for first-in-human dose estimation. It would be useful practically to estimate first-in-human dose for drug development.

• Biomolecules & Therapeutics
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• 제25권6호
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• pp.648-658
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• 2017

7-O-Succinyl macrolactin A (SMA) exerts several pharmacological effects including anti-bacterial, anti-inflammation, and anti-cancer activities. Recently, SMA has been extensively evaluated as an anti-cancer drug. Thus, the objectives of the present study were to characterise the pharmacokinetics of SMA via both non-compartmental and compartmental analysis in mice, rats, and dogs, and to derive an appropriate first-in-man dose based on allometric scaling of the animal data. The time courses of plasma SMA concentrations after intravenous administration to rats and dogs were analysed retrospectively, as were data collected after intraperitoneal SMA injection in mice. Pharmacokinetic parameters were estimated via both noncompartmental and compartmental analysis, and were correlated with body weight and/or the potential maximum life-span. The clearance and distribution volume of SMA in humans were predicted, and a first-in-man dose proposed. A two-compartment model best described the time courses of SMA plasma concentrations after a saturation elimination process was applied to fit the dataset obtained from rats. Incorporation of the maximum potential life-span during allometric scaling was required to improve the estimation of human clearance. The SMA clearance and the distribution volume in the steady state, in a 70-kg adult male, were estimated to be 30.6 L/h and 19.5 L, respectively. To meet the area under the curve (AUC) required for anti-tumour activity, a dose of 100 mg (~1.5 mg/kg) was finally proposed as the first dose for a 70-kg human. Although toxicological profiles derived from non-clinical studies must be considered before any final decision is made, our work will facilitate clinical studies on SMA.

• Nuclear Engineering and Technology
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• 제45권1호
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• pp.1-12
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• 2013

This paper describes the radiation doses to human and non-human biota in the Republic of Korea, as a result of the Fukushima nuclear accident. By using the measured airborne activity and ground deposition, the effective and thyroid doses of five human age groups (infant, 5 years, 10 years, 15 years and adult) were estimated by the ECOSYS code, and the whole body absorbed dose rate of the eight Korean reference animals and plants (RAPs) was estimated by the K-BIOTA (the Korean computer code to assess the risk of radioactivity to wildlife). The first-year effective and thyroid human doses ranged from 5.7E-5 mSv in the infant group to 2.0E-4 mSv in the 5 years group, and from 5.0E-4 mSv in the infant group to 3.4E-3 mSv in the 5 years group, respectively. The life-time (70 years) effective and thyroid human doses ranged from 1.5E-4 mSv in the infant group to 3.0E-4 mSv in the 5 years group, and from 6.0E-4 mSv in the infant group to 3.5E-3 mSv in the 5 years group, respectively. The estimated maximum whole body absorbed dose rate to the Korean RAPs was 6.7E-7 mGy/d for a snake living in soil (terrestrial biota), and 2.0E-5 mGy/d for freshwater fish (aquatic biota), both of which were far less than the generic dose criteria to protect biota from ionizing radiation. Also, the screening level assessment for ERICA's (Environmental Risks from Ionizing Contaminants: Assessments and management) limiting organisms showed that the risk quotient (RQ) for the estimated maximum soil and water activity was significantly less than unity for both the terrestrial and freshwater organisms. Conclusively, the radiological risk of the radioactivity released into the environment by the Fukushima nuclear accident to the public and the non-human biota in the republic of Korea is considered negligible.

• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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• pp.3175-3178
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• 2014

Background: Gastric cancer is a common malignant tumor. Our previous study demonstrated inhibitory effects of 3-bromopyruvate (3-BrPA) on pleural mesothelioma. Moreover, we found that 3-BrPA could inhibit human gastric cancer cell line SGC-7901 proliferation in vitro, but whether similar effects might be exerted in vivo have remained unclear. Aim: To investigate the effect of 3-BrPA to human gastric cancer implant tumors in nude mice. Materials and Methods: Animals were randomly divided into 6 groups: 3-BrPA low, medium and high dose groups, PBS negative control group 1 (PH7.4), control group 2 (PH 6.8-7.8) and positive control group receiving 5-FU. The TUNEL method was used to detect apoptosis, and cell morphology and structural changes of tumor tissue were observed under transmission electron microscopy (TEM). Results: 3-BrPA low, medium, high dose group, and 5-FU group, the tumor volume inhibition rates were 34.5%, 40.2%, 45.1%, 47.3%, tumor volume of experimental group compared with 2 PBS groups (p<0.05), with no significant difference between the high dose and 5-FU groups (p>0.05). TEM showed typical characteristics of apoptosis. TUNEL demonstrated apoptosis indices of 28.7%, 39.7%, 48.7% for the 3-BrPA low, medium, high dose groups, 42.2% for the 5-FU group and 5% and 4.3% for the PBS1 (PH7.4) and PBS2 (PH6.8-7.8) groups. Compared each experimental group with 2 negative control groups, there was significant difference (p<0.05); there was no significant difference between 5-FU group and medium dose group (p>0.05), but there was between the 5-FU and high dose groups (p<0.05). Conclusions: This study indicated that 3-BrPA in vivo has strong inhibitory effects on human gastric cancer implant tumors in nude mice.

• 대한방사선기술학회지:방사선기술과학
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• 제41권3호
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• pp.215-221
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• 2018

Cone beam Computed Tomography(CBCT) is an increasing trend in clinical applications due to its ability to increase the accuracy of radiation therapy. However, this leaded to an increase in exposure dose. In this study, the simulation using Monte Carlo method is performed and the absorbed dose of CBCT is analyzed and standardized data is presented. First, after simulating the CBCT, the photon spectrum was analyzed to secure the reliability and the absorbed dose of the tissue in the human body was evaluated using the MIRD phantom. Compared with SRS-78, the photon spectrum of CBCT showed similar tendency, and the average absorbed dose of MIRD phantom was 8.12 ~ 25.88 mGy depending on the body site. This is about 1% of prescription dose, but dose management will be needed to minimize patient side effects and normal tissue damage.

• 대한방사선기술학회지:방사선기술과학
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• 제47권3호
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• pp.167-173
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• 2024

This study purpose to establish an appropriate target exposure index(EIT) using dose area product(DAP) and exposure index(EI) based on chest radiography. First, the system response experiment was conducted with radiation quality of RQA5 to compare the dosimetry and dose area product of equipment. Next, EI and DAP were acquired and analyzed while varying the dose in the diagnostic at 70kVp using a human body model phantom. The signal to noise ratio(SNR) of the obtained results was analyzed in the diagnostic with in the diagnostic reference level(DRL) application range. The DRL at percentage 25% had a dose of 0.17 mGy and EI was 83, and at percentage 75% the dose was 0.68 mGy and EI was 344. As the dose increased, the SNR in the subdiaphragm increased. To set the EIT, calibration must first be performed using a dosimeter and set within the DRL range to reflect the needs of the medical institution.

• 한국방사선학회논문지
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• 제14권2호
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• pp.169-178
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• 2020

국민의 의료수준 향상으로 CT 검사건수는 매년 증가되고 있는 추세이며, 이에 따라 연간 의료 방사선에 의한 피폭선량 또한 증가되고 있다. 이에 본 연구에서는 CT 부위별 검사 시 노출되는 인체의 유효선량을 평가하고, 이로 인한 생애 암 귀속 위험도를 추정하고자 한다. 첫 번째로, CT 진단참고수준 가이드라인에서 제시하는 부위 중 5가지를 선정하였으며, CT 장치를 통해 각 검사 부위별로 노출되는 인체의 유효선량을 평가하였다. 두 번째로, 동일한 조건 내 ALARA-CT 프로그램을 이용하여 인체 장기 및 유효선량을 산정하였으며, 국내 DRL 수준과 비교하여 검사 프로토콜에 대한 적정성을 평가하였다. 세 번째로, CT 검사 시 노출되는 유효선량에 의한 생애 암 귀속 위험도(LAR)을 추정하였다. 그 결과, 검사 중 복부 다중시기 검사 시 21.18 mSv로 가장 높은 유효선량을 나타내었으며, 복부검사를 제외한 나머지 검사에서는 DRL 이하의 선량수준을 나타내었다. 동일한 조건 내 선량계산 프로그램을 이용한 유효선량 평가 결과, 각 검사별로 약 1.1 ~ 1.9배 이상 높은 결과를 나타내었으며, 장기선량의 경우 검사 부위에 근접한 장기일수록 산란선에 의해 높은 영향을 나타내었다. CT 검사 시 성인의 생애 암 귀속 위험도의 경우, 연령이 증가함에 따라 점차적으로 감소되는 양상을 보였으며, 성별에 따라 다소 상이한 결과를 나타내었다.

• Nuclear Engineering and Technology
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• 제3권3호
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• pp.155-160
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• 1971

중성자 검출기의 교정을 위한 기초자료를 제공할 목적으로 당 연구실에서 보유하고 있는 $^{239}$ Pu-Be, $^{241}$Am-Li 및 241Am-F 중성자선원에 대한 평균 및 유효에너지와 중성자당 등가선량 환산인자를 계산하였다. 이들은 중성자 스펙트럼 및 중성자의 에너지 함수로서 주어진 등가선량에 대한 여러 보고 자료에 따라 수치계산법을 도입하여 구해졌다. 그 계산결과는 $^{239}$ Pu-Be, $^{241}$Am-Li 및 $^{241}$Am-F 순서로 각각 다음과 같이 주어진다 1. 평균에너지 4.07$\pm$0.33, 0.42 및 1.41 MeV; 2. 중성자의 단일충돌과정에 의하여 인체가 받게되는 선량의 개념에 따라 구한 유효에너지 4.45$\pm$0.344, 0.51 및 1.47 MeV； 3. 중성자의 다중충돌과정에 의하여 인체가 받게되는 선량의 개념에 따라 구한 유효에너지 4.50$\pm$0.36, 0.50 및 1.45 MeV； 4. 중성자당 단일충돌 등가선량 환산인자 (2.74$\pm$0.07)$10^{-8}$ , 1.58$\times$ $10^{-8}$ 및 2.34$\times$$10^{-8}$ rems/(n/$\textrm{cm}^2$); 5. 중성자당 다중충돌 등가선량 환산인자 (3.55$\pm$0.09)$10^{-8}$ , 2.19$\times$$10^{-8}$ 및 2.82$\times$$10^{-8}$ rems/(n/$\textrm{cm}^2$).

• Nuclear Engineering and Technology
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• 제38권3호
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• pp.239-250
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• 2006

Computational anthropomorphic phantoms are computer models of human anatomy used in the calculation of radiation dose distribution in the human body upon exposure to a radiation source. Depending on the manner to represent human anatomy, they are categorized into two classes: stylized and tomographic phantoms. Stylized phantoms, which have mainly been developed at the Oak Ridge National Laboratory (ORNL), describe human anatomy by using simple mathematical equations of analytical geometry. Several improved stylized phantoms such as male and female adults, pediatric series, and enhanced organ models have been developed following the first hermaphrodite adult stylized phantom, Medical Internal Radiation Dose (MIRD)-5 phantom. Although stylized phantoms have significantly contributed to dosimetry calculation, they provide only approximations of the true anatomical features of the human body and the resulting organ dose distribution. An alternative class of computational phantom, the tomographic phantom, is based upon three-dimensional imaging techniques such as magnetic resonance (MR) imaging and computed tomography (CT). The tomographic phantoms represent the human anatomy with a large number of voxels that are assigned tissue type and organ identity. To date, a total of around 30 tomographic phantoms including male and female adults, pediatric phantoms, and even a pregnant female, have been developed and utilized for realistic radiation dosimetry calculation. They are based on MRI/CT images or sectional color photos from patients, volunteers or cadavers. Several investigators have compared tomographic phantoms with stylized phantoms, and demonstrated the superiority of tomographic phantoms in terms of realistic anatomy and dosimetry calculation. This paper summarizes the history and current status of both stylized and tomographic phantoms, including Korean computational phantoms. Advantages, limitations, and future prospects are also discussed.

• Food Science and Biotechnology
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• 제18권2호
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• pp.552-555
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• 2009

This study investigated the proapoptotic effect of ethanol extracts obtained from dandelion (Taraxacum officinale) flower on human ovarian cancer SK-OV-3 cells. Cells were treated with dandelion flowers ethanol extract (DFE) ranging from 1.5625 to $100{\mu}g/mL$ for 24 hr. Significant antiproliferative effects of DFE were first observed from at $6.25{\mu}g/mL$ (p<0.05), and this inhibition showed in a dose-dependent manner. When cells were treated with more than $6.25{\mu}g/mL$ DFE, cell-cycle analysis showed that DFE caused an increase in the percentage of sub-G0/G1 cells and arrested at the S and G2/M phase in a dose-dependent manner. Moreover, apoptosis induction by DFE involved p53 activation and bax upregulation as well as downregulation of bcl-2. Our findings indicate that DFE resulted in apoptotic cell death, suggesting that DFE possesses potential anticancer properties.