• Title/Summary/Keyword: Single dose

Search Result 1,843, Processing Time 0.027 seconds

Pharmacokinetics of PEG-Hemoglobin SB1, a Hemoglobin-Based Oxygen Carrier, after Its Intravenous Administration in Beagle Dogs

  • Kwon, Oh-Seung;Chung, Uoo-Tae;Chung, Youn-Bok
    • Archives of Pharmacal Research
    • /
    • v.27 no.2
    • /
    • pp.259-264
    • /
    • 2004
  • The purpose of the present study was to investigate the pharmacokinetics of PEG-hemoglobin SB 1, a modified bovine hemoglobin with polyethylene glycol, after its single and multiple administration in beagle dogs. For this purpose, the analytical method of free hemoglobin in the plasma was developed and validated. Excellent linearity ($r^2$=0.999) was observed in the calibration curve data, with the limit of quantification of 0.005 g/dL. The precision and the deviation of the theoretical values for accuracy were always within $\pm$15% in both the between-and the within-day results. The method was tested by measuring the plasma concentrations following intravenous administration to beagle dogs and was shown to be suitable for pharmacokinetic studies. In a single dose study, the plasma half-life (t$_{1}$2/) increased and the total body clearance (Cl$_{t}$) decreased with the dose (i.e., 0.017 to 0.75 gHb/kg as PEG-hemoglobin SB1) in both sexes. The volume of distribution at steady-state (Vd$_{ss}$ ) showed no difference with the dose. In contrast, the values of t$_{1}$2/, CL$_{t}$ and the area under the plasma concentration-time curve (AUC) after the multiple dose were significantly different from those of the single dose administration. The values of t$_{1}$2/ in the multiple administration were about two times higher-than that of the single dose. As a result, t$_{1}$2/ of hemoglobin after the administration of PEG-hemoglobin SB1 was about 15-30 h, indicating the PEG modification of the hemoglobin lead to a prolongation of plasma concentration of the protein. Therefore, these observations suggested that the PEG modification of hemoglobin is potentially applicable in the hemoglobin-based therapeutics.tics.

Single oral toxicity test and safety classification for Kaempferia parviflora (흑생강의 단회투여독성시험과 안전성등급화)

  • Han, Young-Hoon;Park, Yeong-Chul
    • The Korea Journal of Herbology
    • /
    • v.33 no.4
    • /
    • pp.53-58
    • /
    • 2018
  • Objectives : Kaempferia parviflora Rhizome is black ginger indigenous to Laos and Thailand. It has been used as a folk medicine to improve blood flow and promote vitality and longevity with good health and well being. For these reasons, Kaempferia parviflora Rhizome has been focused on developing it as a food or food supplement. In addition, Kaempferia parviflora Rhizome could be under consideration of new prescription based on its characteristic compounds, polymethoxyflavonoids. However, it needs to be certified as safe before it can be used. Here, a single-oral toxicity test and safety classification was carried out to identity acute information of the toxicity of Kaempferia parviflora Rhizome powder and to make sure of its safety in clinical applications. Methods : Test substance was orally administered to male and female SD-rat at dose levels of 5000 mg/kg to estimate approximate lethal dose(ALD). Based on the acute information of the toxicity, the safety classification was estimated using the HED(human equivalent dose)-based MOS(margin of safety). Results : At 14 days after treatment with test substance. there were no of test substance related with mortalities and clinical signs. In addition, no changes in the body or organ weights and no gross or histopathological findings were observed. Thus, the ALD of Kaempferia parviflora Rhizome powder was considered over 5,000 mg/kg in both female and male mice. Conclusions : Based on the single oral toxicity test using the highest and limit dose, 5,000 mg/kg and the decision guideline for safety classification based on HED-based MOS, it was estimated that Kaempferia parviflora Rhizome powder is classified as "Specified class B" indicating that clinical dose is not limited to patients as safe as food.

Organogenesis by Combined-Dose of Activin A and IGF-1 In Xenopus Presumptive Ectoderm (Xenopus 예정외배엽에서 Activin A와 IGF-1의 복합처리에 의한 기관분화)

  • 정선우;이호선;윤춘식
    • Journal of Life Science
    • /
    • v.9 no.5
    • /
    • pp.504-509
    • /
    • 1999
  • The trend of organogenesis in Xenopus presumptive ectoderm was studied by combined dose of activin A and IGF-1(insulin-like growth factor-1). In reference study of Asashima and his colleagues, the inductive patterns of various organs were reported with activin, the potent mesoderm inducing factor. In present study, the inducing pattern was cleared with combined-dose of concentration 1-100 ng/ml activin A and IGF-1. In addition, the result from single treatment of activin A was compared with former study. As a result, eye was differentiated in 5-20% of explants at 10 and 50 ng/ml concentrative combination of activin A. Otic vesicle was appeared in the entire concentrative combination of IGF-1. Pronephric duct was induced 19-38% of explants at the concentration of activin A 100 ng/ml by adding IGF-1. The comparison of single treatment of activin A was showed some difference in dose-dependent inducing pattern.

  • PDF

SINGLE OR FOUR-WEEK REPEATED INTRAVENOUS TOXICITY STUDIES OF A NEW CEPHALOSPORIN ANTffiIOTIC AGENT, IDC-7181 IN RATS

  • Zhang, Hu-Song;Huang, Zai-Zhi;Jung, Eun-Yong;Jung, Seong-Eui;Lim, Kwang-Hyun;In, Chang-Hoon;Kim, Dae-Joong;Nam, Sang-Yoon;Kang, Jong-Koo
    • Proceedings of the Korean Society of Toxicology Conference
    • /
    • 2001.10a
    • /
    • pp.169-169
    • /
    • 2001
  • This study was designed to evaluate an acute and subacute intravenous dose toxicity of a new cephalosporin antibiotic agent, IDC-7181 in 7-week-old Sprague-Dawley rats. IDC-7181 was intravenously injected to rats at dose levels of 0, 3.2, 16, 80, 400 and 2, 000 mg/kg/day for single dose toxicity study and at dose levels of 0, 10, 50 and 250 mg/kg/day for 4 week-repeated dose toxicity study. All rats survived throughout the study periods.(omitted)

  • PDF

Application of Single Cell Gel Electrophoresis for Detection of DNA Single Strand Breaks in DNA of Fish Blood Cell (어류혈구세포에 있어서 Single Cell Gel Electrophoresis를 응용한 DNA Single Strand Breack의 측정)

  • KIM Gi Beum;LEE Richard F.;MARUYA Keith A.
    • Korean Journal of Fisheries and Aquatic Sciences
    • /
    • v.36 no.4
    • /
    • pp.346-351
    • /
    • 2003
  • Single-cell gel electrophoresis (comet assay) was used to detect DNA single strand break in blood cells from several marine fish species. Three fish species were collected from Georgia coastal area. Mummichog, Fundulus heteroclitus showed higher DNA damage than sea bass, Lateolabrax japonicus and trout, Oncorhynchus masou masou under the same experimental conditions. Mummichogs had more alkaline-labile sites on their DNA than other fish species. The comet assay with mummichog blood cells at pH 12.5 showed a dose-response curve with the increasing concentrations of hydrogen peroxide. While the isolated leucocytes showed no increase of DNA damage after in vitro exposure to 2-methyl-1,4-naphthoquinone (MNQ), erythrocytes showed dose-dependent DNA damage. These results indicate that the comet assay can be applied successfully as a bioassay using erythrocyte for environmental monitoring.

Study of Single-dose Toxicity of Guseonwangdo-go Glucose Intramuscular Injection in Sprague-Dawley Rats

  • Jo, Su-Jeong;Kim, Sung-Chul;Kim, Yu-Jong;Kim, Eun-Jung;Kim, Kap-Sung;Lee, Seung-Deok
    • Journal of Pharmacopuncture
    • /
    • v.17 no.1
    • /
    • pp.51-58
    • /
    • 2014
  • Objectives: This study was performed to analyze single-dose intramuscular toxicity of Guseonwangdo-go glucose pharmacopuncture. Methods: Eighty six-week-old Sprague-Dawley rats were divided into two large groups of forty rats; Guseonwangdo-go glucose 5% and Guseonwangdo-go glucose 20% groups. Each group was sub-divided into four smaller groups of five males and five females, with the following dosages of pharmacopuncture being administered by intramuscular (IM) injection in each group: group 1 (G1, control group): 1.0 mL of normal saline solution, group 2 (G2, low-dose group): 0.1 mL, group 3 (G3, mid-dose group): 0.5 mL, and group 4 (G4, high-dose group): 1.0 mL. Results: No mortalities or clinical signs were observed in any group. Also, no significant changes in body weights or in hematological/biochemical analyses were observed between the control and the experimental groups during necropsy or histopathology. Conclusion: The above findings suggest that the lethal dose of Guseonwangdo-go glucose 5% and 20% pharmacopuncture administered via IM injection is more than 1.0 mL per animal in both male and female rats. Further studies on the repeated-dose toxicity of Guseonwangdo-go glucose should be conducted to yield more concrete data.

Toxicity and Safety Profiles of Methanolic Extract of Pistacia integerrima J. L. Stewart ex Brandis (PI) for Wistar Rats

  • Sharwan, Gotmi;Jain, Parag;Pandey, Ravindra;Shukla, Shiv Shankar
    • Journal of Pharmacopuncture
    • /
    • v.19 no.3
    • /
    • pp.253-258
    • /
    • 2016
  • Objectives: The goals of this research were to evaluate acute (single-dose) and sub-acute (repeated-dose) toxicity profiles of methanolic extract of Pistacia integerrima J. L. Stewart ex Brandis (PI) for Wistar rats and to assess the safety profile of PI by observing physiological changes, mortality, changes in body weight, the histopathology of body organs, the hematology and the biochemistry of the animals. Methods: The toxicity profile of PI was evaluated using Wistar rats of both sexes. Animals were divided into four groups: Group 1; control group (normal saline), Group 2; PI-1 (250 mg/kg), Group 3; PI-2 (500 mg/kg), Group 4; PL-3 (1,000 mg/kg). An acute-toxicity study in which animals received a single dose of PI extract (2,000 mg/kg) and were then observed for 14 days for changes in skin, fur, eye color, mucous membrane secretions and excretions, gait, posture, and tonic or clonic movements was performed according to guideline 425 of the Organization of Economic and Corporation Development (OECD). In the repeated-dose toxicity study (OECD - 407) animals received a daily dose of PI extract for 28 days (4 weeks). The parameters observed in this study include body weight, hematology and biochemistry of the animals. Results: In the acute toxicity study, no mortalities or changes in behavior were noted in the animals. The repeated-dose toxicity study was also devoid of any toxicity in the animals during the 28 days of testing with PI extract. The extract did not alter- the body weight, hematology or biochemistry of the animals. The methanolic extract of PI was to be found safe to the no-observed-adverse-effect-level (NOAEL) for the single-dose and repeated-dose toxicity tests in rats. Conclusion: The methanolic extract of PI was devoid of toxicity; hence, it can be used for various ayurvedic preparations and treatments of diseases.

Single-Dose Toxicity and Four Week Repeated-Dose Toxicity Study on Tensolin-F® (3,9-diferuloyl-6-oxopterocarpen) (Tensolin-F® (3,9-diferuloyl-6-oxopterocarpen)의 단회 독성시험 및 4주 반복투여 독성시험)

  • Kim, Keun-Su;Park, Sung-Min;Lee, Nam-Jin;Pyo, Hyeong-Bae;Chai, Hee-Yul;Jung, Yu-Ri;Lin, Chun-Mai;Kim, Sun-Hee;Lee, Hye-Young;Kang, Jong-Koo
    • Toxicological Research
    • /
    • v.23 no.4
    • /
    • pp.405-413
    • /
    • 2007
  • This study was to investigate single and repeated-dose toxicities of Tensolin-$F^{(R)}$, an anti-wrinkle agent, in Sprague-Dawley (SD) rats or ICR mice. In single-dose oral toxicity study, the test materials were administered once by gavage to male and female SD rats at dose levels of 0 and 2,000 mg/kg. No dead animals and abnormal necropsy findings were found in control and Tensolin-$F^{(R)}$ treated group. Therefore, the approximate lethal dose of Tensolin-$F^{(R)}$ was considered to be higher than 2,000 mg/kg in rats. In the 4-week repeated oral toxicity study, the test material was administered once daily by gavage to male and female ICR mice at dose levels of 0, 25, 50 and 100 mg/kg/day for 4-weeks. In the results, no abnormality was observed in mortality, clinical findings, body weight changes, food and water consumptions, opthalmoscopic findings, necropsy findings, histopathological findings. In hematological analysis, there was a trend of increase in reticulocyte at male 25 mg/kg, although such changes were in normal ranges. On the other hand, there was a trend of decrease in hemoglobin at female 50, 100 mg/kg, such changes were in normal ranges. In addition, serum biochemical parameters including sodium, BUN and chloride increased at 25, 50 and 100 mg/kg. Relative organ weights of right testis, brain, lung and left epididymis were increased in 100 mg/kg groups of male rats in contrast to not change in female groups. However, these changes of relative organ weights, hematological and serum biochemical parameters were not accompanied with related signs such as histopathological changes or clinical findings. In conclusion, 4-week repeated oral dose of Tensolin-$F^{(R)}$ to ICR mice did not cause apparent toxicological change at the dose of 25, 50, 100 mg/kg body weight. Consequently the no-observed-adverse-effect level (NOAEL) for Tensolin-$F^{(R)}$ in ICR mice following gavage for at least 4-week is higher than 100 mg/kg/day.

A proposal on multi-agent static path planning strategy for minimizing radiation dose

  • Minjae Lee;SeungSoo Jang;Woosung Cho;Janghee Lee;CheolWoo Lee;Song Hyun Kim
    • Nuclear Engineering and Technology
    • /
    • v.56 no.1
    • /
    • pp.92-99
    • /
    • 2024
  • To minimize the cumulative radiation dose, various path-finding approaches for single agent have been proposed. However, for emergence situations such as nuclear power plant accident, these methods cannot be effectively utilized for evacuating a large number of workers because no multi-agent method is valid to conduct the mission. In this study, a novel algorithm for solving the multi-agent path-finding problem is proposed using the conflict-based search approach and the objective function redefined in terms of the cumulative radiation dose. The proposed method can find multi paths that all agents arrive at the destinations with reducing the overall radiation dose. To verify the proposed method, three problems were defined. In the single-agent problem, the objective function proposed in this study reduces the cumulative dose by 82% compared with that of the shortest distance algorithm in experiment environment of this study. It was also verified in the two multi-agent problems that multi paths with minimized the overall radiation dose, in which all agents can reach the destination without collision, can be found. The method proposed in this study will contribute to establishing evacuation plans for improving the safety of workers in radiation-related facilities.

Hair-Growth Effect and Single Dose Oral Toxicity Test of Illite Powder (Illite 분제 원액의 육모 활성 시험 및 단회 투여 경구 독성시험)

  • 박형섭;임동술;정재훈;이충재;김박광
    • Biomolecules & Therapeutics
    • /
    • v.9 no.4
    • /
    • pp.307-310
    • /
    • 2001
  • The hair-growth effect of Illite was suggested by some people who were using Illite as a beautifying material. We investigated the hair-growth effect of Illite powder. The hair-growth effects were investigated by two methods; the activity of hair-growth after shaving the hairs on the black mouse (C57BL/6) and the recovery activity of hair-growth after hair-loss induced by cyclophosphamide treatment. Suspension of Illite powder was applied to the back of the black mouse by method of skin paste. Illite promoted significantly the hair growth of mouse in both conditions of shaving and hair-loss. And then we investigated the toxicity which may be induced by Illite when it was administrated orally as a single dose. We could not fond out any significant toxicity induced by single dose oral administration of Illite.

  • PDF