• 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.

• Radiation Oncology Journal
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• v.2 no.2
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• pp.261-270
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• 1984

The intrauterine irradiation is essential to achieve adequate tumor dose to central tumor mass of uterine malignancy in radiotherapy. The complications of pelvic organ are known to be directly related to radiation dose and physical parameters. The simulation radiation and medical records of 203 patients who were treated with intrauterine irradiation from Feb. 1983 to Oct. 1983, were critically analized. The physical parameters to include distances between lateral walls of vaginal fornices, longitudinal and lateral angles of tandem applicator to the body axis, the distance from the external os of uterine cervix to the central axis of ovoids were measured for low dose rate irradiation system and high dose rate remote control afterloading system. The radiation doses and dose distributions within cervical area including interesting points and bladder, rectum, according to sources arrangement and location of applicator, were estimated with personal computer. Followings were summary of study results ; 1. In distances between lateral walls of vaginal fornices, the low dose rate system showed as $4\~7cm$ width and high dose rate system showed as $5\~6cm$. 2. In horizontal angulation of tandem to body axis, the low dose rate system revealed mid position$64.6\%$, left deviation $19.2\%$and right deviation $16.2\%$. 3. In longitudinal angulation of tandem to body axis, the mid position was $11.8\%$ and anterior angulation $88.2\%$ in low dose rate system but in high dose rate system, anterior angulation was $98.5\%$. 4. Down ward displacement of ovoids below external os was only $3\%$ in low dose rate system and $66.7\%$ in high dose rate system. 5. In radiation source arrangement, the most activities of tandem and ovoid were 35 by 30 in low dose rate system but 50 by 40 in high dose rate system. 6. In low and high dose rate system, the total doses an4 TDF were 50, 70 Gy and 141, 123, including 40 Gy external irradiation. 7. The doses and TDF in interesting points Co, B, were 93, 47 Gy and 230, 73 in high dose rate system but in low doss rate system, 123, 52 Gy and 262, 75 respectively. 8. Doses and TDF in bladder and rectum were 70, 68 Gy and 124, 120 in low dose rate system, but in high dose rate system, 58, 64 Gy 98, 110 respectively, and then grades of injuries in bladder and rectum were 25, $30\%$ and 18, $23\%$ respectively.

• Progress in Medical Physics
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• v.25 no.2
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• pp.79-88
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• 2014

The dose distributions within the real volumes of tumor targets and critical organs during internal target volume-based intensity-modulated radiation therapy (ITV-IMRT) for liver cancer were recalculated by applying the effects of actual respiratory organ motion, and the dosimetric features were analyzed through comparison with gating IMRT (Gate-IMRT) plan results. The ITV was created using MIM software, and a moving phantom was used to simulate respiratory motion. The doses were recalculated with a 3 dose-volume histogram (3DVH) program based on the per-field data measured with a MapCHECK2 2-dimensional diode detector array. Although a sufficient prescription dose covered the PTV during ITV-IMRT delivery, the dose homogeneity in the PTV was inferior to that with the Gate-IMRT plan. We confirmed that there were higher doses to the organs-at-risk (OARs) with ITV-IMRT, as expected when using an enlarged field, but the increased dose to the spinal cord was not significant and the increased doses to the liver and kidney could be considered as minor when the reinforced constraints were applied during IMRT plan optimization. Because the Gate-IMRT method also has disadvantages such as unsuspected dosimetric variations when applying the gating system and an increased treatment time, it is better to perform a prior analysis of the patient's respiratory condition and the importance and fulfillment of the IMRT plan dose constraints in order to select an optimal IMRT method with which to correct the respiratory organ motional effect.

• Journal of Radiation Protection and Research
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• v.31 no.4
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• pp.165-171
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• 2006

In Korea, a real-time effective dose measurement system is in development. The system uses 32 high-sensitivity MOSFET dosimeters to measure radiation doses at various organ locations in an anthropomorphic physical phantom. The MOSFET dosimeters are, however, mainly made of silicon and shows some degree of energy and angular dependence especially for low energy photons. This study determines the correction factors to correct for these dependences of the MOSFET dosimeters for accurate measurement of radiation doses at organ locations in the phantom. For this, first, the dose correction factors of MOSFET dosimeters were determined for the energy spectrum in the steam generator channel of the Kori Nuclear Power Plant Unit #1 by Monte Carlo simulations. Then, the results were compared with the dose correction factors from 0.652 MeV and 1.25 MeV mono-energetic photons. The difference of the dose correction factors were found very negligible $(\leq1.5%)$, which in general shows that the dose corrections factors determined from 0.662 MeV and 1.25 MeV can be in a steam general channel head of a nuclear power plant. The measured effective dose was generally found to decrease bit $\sim7%$ when we apply the dose correction factors.

• Journal of radiological science and technology
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• v.40 no.1
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• pp.57-62
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• 2017

The purpose of this study is to reconstruct the treatment plan by applying CBCT and DIR to dose changes according to the change of the patient's motion and breast shape in the large breast cancer patients and to compare the doses using TWF, FIF and IMRT. CT and CBCT were performed with MIM6 to create DIRCT and each treatment plan was made. The patient underwent computed tomography simulation in both prone and supine position. The homogeneity index (HI), conformity index (CI), coverage index (CVI) to the left breast as planning target volume (PTV) were determined and the doses to the lung, heart, and right breast as organ at risk (OAR) were compared by using dose-volume histogram and the unique property of each organ. The value of HI of the PTV breast increased in all treatment planning methods using DIRCT, and CVI and CI were decreased in the treatment planning methods using DIRCT.

• Clinical and Experimental Reproductive Medicine
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• v.14 no.1
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• pp.61-70
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• 1987

This study was carried out to investigate the effects of the antiestrogens, LY-117018 and tamoxifen on reproductive organ of ovariectomized immature rats and also to elucidate the mechanism of action of said compounds by bioassay. Each of LY-117018, tamoxifen and estradiol-17${\beta}$ was administered to ovariectomized immature rats at various dose levels. Forty hours after drug administration, tested rats were sacrificed and uterine wet weight, DNA and RNA contents in uterine and liver tissues were investigated. At the same time, uterine wet weight was also investigated with some other rats treated with 125${\mu}g$ of LY-117018 together with increasing doses of tamoxifen. Ovariectomized immature rats given 25${\mu}g$ single dose of each drug were sacrificed on Day 1, 2, 3, 4, and 5 after drug administration and uterine was weighed to estimate the duration of action of LY-117018 and tamoxifen. The results were summarized as follows: 1. The administration of LY-117018 or tamoxifen to ovariectomized rats increased uterine wet weight and DNA and RNA contents in uterine tissues with more increase in tamoxifen groups, but significant differences between groups treated at dose levels of 5${\beta}$ or more of both drugs were observed. Estradiol-17${\beta}$ groups showed significant increases in each group(P<0.01). 2. The administration of LY-117018 or tamoxifen to each group significantly increased DNA and RNA contents in liver tissues with more increase in tamoxifen groups. Estradiol-17${\beta}$ groups showed no significant differences between treatment groups of 5${\beta}$ or more. 3. Treatment with 125${\beta}$ of LY-117018 together with various doses of tamoxifen resulted in more increase of uterine wet weight than treatment with a single dose of LY-117018 or tamoxifen. 4. Treatment with 0.2${\beta}$ of LY-117018 or tamoxifen in ovariectomized rats decreased uterine wet weight,DNA and RNA contents in liver and uterine tissues compared with ovariectomized control. 5. The duration of effective action of LY-1l7018 and tamoxifen was 4 days or more. 6. There was significant difference(P<0.001) in uterine wet weight between Day 9after ovariectomy (two days after LY-117018 or tamoxifen treatment) and Day 10(63.7${\pm}$3.5mg, 39.2${\pm}$9.9mg, respectively).

• Biomolecules & Therapeutics
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• v.14 no.4
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• pp.253-258
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• 2006

LDD175(4-choloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-l-carboxylic acid) is one of benzofuroindole derivatives that act as a potent $BK_{Ca}$ channel openers. In the process of testing LDD175 as a new drug candidate, an acute toxicity study was carried out in mice. The mice were administered LDD175 intraperitoneally at dose of 0.2, 1, 10, 50, 100, 200, 400, 800mg/kg and orally at dose of 10, 100, 400, 800mg/kg body weight. After administering LDD175, the vital organs such as the liver, kidney and spleen were carefully observed for any significant pathological features or differences from the norm over a l4-day period. LDD175 did not induce any short-term toxicity at doses less than 100mg/kg. A $LD_{50}$ of LDD175 was 2493mg/kg in male mice and 4908mg/kg in female mice. Weight reduction was observed at a dose of 800mg/kg in male, and 400 and 800mg/kg in female. The kidney weight decreased in females after an intraperitoneal injection of LDD175 high dose(>400mg/kg, i.p.), and the spleen weight increased in the male(800mg/kg, i.p.) and female(400mg/kg, i.p.) mice. Inspite of the change in organ weights, there were neither histopathological changes nor any gross morphological abnormalities detected in any organ. LDD175 did not produce significant changes in the general behavior at doses of <200mg/kg, but decreased locomotor activity was observed at an intraperitoneal dose of 400mg/kg. Its effects on the locomotor activity and activity on the rotarod were tested and compared with the effects of diazepam 5mg/kg. The decrement in the locomotor activity and the activity on the rotarod induced by LDD175 was less serious than it by diazepam.

• The Korea Journal of Herbology
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• v.36 no.5
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• pp.101-108
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• 2021

Objectives : A root of Dipsacus asperoides C. Y. Cheng et T. M. Ai (D. asperoides) has been traditionally used as a medicinal resource in several Asian countries, including Korean and traditional Chinese medicine that has been traditionally used for treating several medical conditions including pain, arthritis, and bone fractures in Korea. In the present study, we investigated potential subacute toxicities of D. asperoides extract. Methods : C57BL/6 mice (male, 7weeks) were randomly divided into 4 groups of 5 mice. Except for the control group, the mice were orally administrated D. asperoides extract at doses of 50, 150, or 450 mg/kg/day for 2 weeks. At the end of the treatment period, all mice were euthanized, and the following parameters were examined: mortality, body weight, clinical signs, gross findings, hematology, serum biochemistry, organ weight, and histopathology. Results : There were no abnormalities in mortality, clinical signs, body weight, gross findings, or organ weight after repeated administration of D. asperoides extract for 2 weeks, compared with the control group. In addition, there were no significant changes in hematological, serum biochemical, and histopathological parameters between the control group and D. asperoides extract administrated groups with doses of up to 450 mg/kg/day. Conclusion : In this study, D. asperoides extract showed no significant toxicities at a dose of up to 450 mg/kg/day in mice. Although we could not confirm the toxic dose of D. asperoides extract, it can be considered safe for further pharmacological use.

• Biomolecules & Therapeutics
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• v.23 no.3
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• pp.296-300
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• 2015

${\beta}$-Lapachone has drawn increasing attention as an anti-inflammatory and anti-cancer drug. However, its oral bioavailability has not been yet assessed, which might be useful to develop efficient dosage forms possibly required for non-clinical and clinical studies and future market. The aim of the present study was thus to investigate pharmacokinetic properties of ${\beta}$-lapachone as well as its first-pass metabolism in the liver, and small and large intestines after oral administration to measure the absolute bioavailability in rats. A sensitive HPLC method was developed to evaluate levels of ${\beta}$-lapachone in plasma and organ homogenates. The drug degradation profiles were examined in plasma to assess the stability of the drug and in liver and intestinal homogenates to evaluate first-pass metabolism. Pharmacokinetic profiles were obtained after oral and intravenous administration of ${\beta}$-lapachone at doses of 40 mg/kg and 1.5 mg/kg, respectively. The measured oral bioavailability of ${\beta}$-lapachone was 15.5%. The considerable degradation of ${\beta}$-lapachone was seen in the organ homogenates but the drug was quite stable in plasma. In conclusion, we suggest that the fairly low oral bioavailability of ${\beta}$-lapachone may be resulted from the first-pass metabolic degradation of ${\beta}$-lapachone in the liver, small and large intestinal tracts and its low aqueous solubility.

• Toxicological Research
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• v.21 no.2
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• pp.161-165
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• 2005

Bisphenol A (SPA), a environmental endocrine disruptor, is considered to bind to estrogen receptors and to regulate the expressions of estrogen responsive genes. This study was to evaluate the effect of SPA administration on body weight, sex ratio and litter size on 18 days in prenatal periods, the effect of reproductive organ weight and blood hematological values on 24 days postpartum in pregnant mice. The female mice was administrated to low doses of SPA (0, 0.05, 0.5 and 5.0 mg/kg B.W.) by intraperitoneal injection in gestation days $0\~15$ with 5 times at 3 days interval. The maternal body weight, litter size and sex ratios were similar to in all experimental groups, but body weights of male and female offspring was significantly lower in 5.0mg SPA group when compared to any other groups (P<0.05). No treatment-related effects on body weight, ovary weight and blood hematological values were observed in dams on 24 days after delivery. The uterine weight in 5.0mg SPA group was slightly higher than those of any other groups, but not significantly difference. The histological evaluation of ovary in dam mice on 24 days after dilivery was not difference in all experimental groups, but the endometriosis of uterus in dam mice were significantly increased in 0.5mg SPA group when compared to control group. These results indicates that low concentration of SPA should not be considered as a selective reproductive toxicant.