• Title/Summary/Keyword: Multiple-dose

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Effect of Korean Red Ginseng extracts on drug-drug interactions

  • Kim, Se-Jin;Choi, Seungmok;Kim, Minsoo;Park, Changmin;Kim, Gyu-Lee;Lee, Si-On;Kang, Wonku;Rhee, Dong-Kwon
    • Journal of Ginseng Research
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    • v.42 no.3
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    • pp.370-378
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    • 2018
  • Background: Ginseng has been the subject of many experimental and clinical studies to uncover the diverse biological activities of its constituent compounds. It is a traditional medicine that has been used for its immunostimulatory, antithrombotic, antioxidative, anti-inflammatory, and anticancer effects. Ginseng may interact with concomitant medications and alter metabolism and/or drug transport, which may alter the known efficacy and safety of a drug; thus, the role of ginseng may be controversial when taken with other medications. Methods: We extensively assessed the effects of Korean Red Ginseng (KRG) in rats on the expression of enzymes responsible for drug metabolism [cytochrome p450 (CYP)] and transporters [multiple drug resistance (MDR) and organic anion transporter (OAT)] in vitro and on the pharmacokinetics of two probe drugs, midazolam and fexofenadine, after a 2-wk repeated administration of KRG at different doses. Results: The results showed that 30 mg/kg KRG significantly increased the expression level of CYP3A11 protein in the liver and 100 mg/kg KRG increased both the mRNA and protein expression of OAT1 in the kidney. Additionally, KRG significantly increased the mRNA and protein expression of OAT1, OAT3, and MDR1 in the liver. Although there were no significant changes in the metabolism of midazolam to its major metabolite, 1'-hydroxymidazolam, KRG significantly decreased the systemic exposure of fexofenadine in a dose-dependent manner. Conclusion: Because KRG is used as a health supplement, there is a risk of KRG overdose; thus, a clinical trial of high doses would be useful. The use of KRG in combination with P-glycoprotein substrate drugs should also be carefully monitored.

BISPHOSPHONATE(ZOLEDRONIC ACID) RELATED OSTEOMYELITIS ON MANDIBLE-A CASE REPORT (Bisphosphonate(Zoledronic acid)와 연관된 하악골의 골수염-증례보고)

  • Lee, Su-Youn;Choi, So-Young;Kim, Jin-Wook;Kwon, Tae-Geon;Jang, Hyung-Jung;Kim, Chin-Soo;Lee, Sang-Han
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.30 no.4
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    • pp.395-398
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    • 2008
  • Bisphosphonate are a class of drugs with a chemical structure which inhibit bone resorption, actually used for metastatic bone disease, osteoporosis, Paget's disease and multiple myeloma. Significant complication associated with their use is reported recently : mandibular and maxillary osteomyelitis or osteonecrosis. So we here report our case about the patient who was diagnosed of prostate cancer in 2004 April and treated with bisphosphonate(Zoledronic acid-$Zometa^{(R)}$, Novartis Co.) intravenously every 3 to 4weeks at a dose of 4mg to prevent bone metastasis, and also, the patient who came to the hospital due to the bony exposure of mandible and pain in 2006 November and was diagnosed osteomyelitis of mandible as a result of biopsy, bone scan, PET CT examination.

Anti-Allergic Effects of Nodakenin in IgE/Ag-Induced Type I Hypersensitivity (노다케닌의 항 알러지 효과)

  • Kim, Yong-Jae;Park, Sae-Jin;Kim, Tack-Joong
    • Journal of Life Science
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    • v.21 no.12
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    • pp.1721-1725
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    • 2011
  • Mast cells are major effector cells associated with allergic responses. They are activated through the release of histamine, arachidonic acid, and proinflammatory cytokines. We investigated the effect of nodakenin, derived from the roots of Angelica gigas Nakai, on mast cell degranulation and on an allergic response in an animal model. We also investigated the effect of nodakenin on expression of multiple cytokines. Nodakenin suppressed the release of ${\beta}$-hexosaminidase, a marker of degranulation, as well as the expression of interleukin IL-4 and TNF-${\alpha}$ mRNA. Nodakenin inhibited the passive cutaneous anaphylaxis (PCA) reaction in ICR mice in a dose-dependent manner. These results suggest that nodakenin can inhibit mast cell degranulation through the inhibition of IL-4 and TNF-${\alpha}$ mRNA expression, and that nodakenin may potentially serve as an anti-allergic agent.

Effect on Computerized Neurobehavioral Test Performance of the Car Painters Exposed to Organic Solvents (자동차 페인트 도장공에 있어서 컴퓨터를 이용한 신경행동검사 수행기능의 평가)

  • Sa, Kong-Joon;Chung, Jong-Hak
    • Journal of Preventive Medicine and Public Health
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    • v.27 no.3 s.47
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    • pp.487-504
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    • 1994
  • A cross-sectional study was performed to evaluate the effects of chronic low-dose solvent on neurobehavioral performance of 118 male car painters. A control group of 113 workers matched for age was selected from different sections of the factory. The mean age and the mean duration of employment were 33 years and 6.7 years in both groups. Mean years of education were 11.4 years in car painters and 11.8 years in controls. Each worker completed a medical and occupational questionnaire and four tests of Swedish performance evaluation system. These included simple reaction time, symbol digit, digit span and finger tapping speed. Althougth the mean duration of employment was 6.7 years, comparison of mean performance showed a significantly poorer performance on simple reaction time (p<0.05), symbol digit(p<0.01) and digit span(p<0.05) in car painters. In univariate analysis, age and educational level contributed to poorer performance on symbol digit and digit span. Smoking appeared to slow finger tapping speed in car painters. Performance of four tests of car painters exposed to high level of solvent was poorer than that of car painters exposed to low level. In multiple regression models, controlling for age, alcohol, smoking and shift work, solvent exposure was found to be associated with performance of simple reaction time, symbol digit and digit span and exposure to high level of solvent was related to poorer performance of symbol digit and digit span.

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Bioequivalence Approaches for Highly Variable Drugs: Issue and Solution (개체 변이가 큰 약물 (highly variable drug)의 생물학적동등성 시험을 위한 실험설계 및 평가방법)

  • Baek, In-Hwan;Seong, Soo-Hyeon;Kwon, Kwang-Il
    • Korean Journal of Clinical Pharmacy
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    • v.19 no.1
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    • pp.50-60
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    • 2009
  • Highly variable drugs (within-subject variability greater than 30%) have been difficult to meet current regulatory acceptance criteria using a reasonable number of study subjects. In this study, we reviewed previous studies presenting alternative approaches for bioequivalence evaluation of highly variable drugs, and focused on an approach for widening the bioequivalence acceptance limits using within-subject variability. We discussed the suggested five solutions for highly variable drug including the deletion of $C_{max}$ of the bioequivalence criteria, direct expansion of bioequivalence limit, multiple dose studies in steady state, bioequivalence assessment on the metabolite, add-on study, and widening the bioequivalence acceptance limits based on reference variability. The methods for widening of bioequivalence limits based on reference variability are scaled average bioequivalence containing within-subject variability on reference drug (${\sigma}_{WR}$), population bioequivalence derived from total variability on reference drug (${\sigma}_{TR}$) and test drug (${\sigma}_{TT}$), and individual bioequivalence derived from subject by formulation interaction variability (${\sigma}_D$) and within subject variability on reference drug (${\sigma}_{WR}$) and test drug (${\sigma}_{TR}$). To apply these methods, the switching variability (${\sigma}_0$) will have to be set by the regulatory authorities. The proposals of bioequivalence evaluation approach for the highly variable in Korea are presented for both of new drug and reevaluation drug.

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Long-term cosmesis following a novel schedule of accelerated partial breast radiation in selected early stage breast cancer: result of a prospective clinical trial

  • Sayan, Mutlay;Hard, Daphne;Wilson, Karen;Nelson, Carl;Gagne, Havaleh;Rubin, Deborah;Heimann, Ruth
    • Radiation Oncology Journal
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    • v.35 no.4
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    • pp.325-331
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    • 2017
  • Purpose: There is controversy regarding the cosmetic outcome after accelerated partial breast radiation (APBR). We report the cosmetic outcome from a single-arm prospective clinical trial of APBR delivered using intensity-modulated radiation therapy (IMRT) in elderly patients with stage I breast cancer (BC), using a novel fractionation schedule. Materials and Methods: Forty-two patients aged ${\geq}65$, with Stage I BC who underwent breast-conserving surgery were enrolled in a phase I/II study evaluating a 2-week course of APBR. Thirty eligible patients received 40 Gy in 4 Gy daily fractions. Cosmetic outcome was assessed subjectively by physician/patient and objectively by using a computer program (BCCT.core) before APBR, during, and after completion of the treatment. Results: The median age was 72 years, the median tumor size was 0.8 cm, and the median follow-up was 50.5 months. The 5-year locoregional control in this cohort was 97% and overall survival 87%. At the last follow-up, patients and physicians rated cosmesis as 'excellent' or 'good' in 100% and 91 %, respectively. The BCCT.core program scored the cosmesis as 'excellent' or 'good' in 87% of the patients at baseline and 81% at the last follow-up. The median $V_{50}$ (20 Gy) of the whole breast volume (WBV) was 37.2%, with the median WBV $V_{100}$ (40 Gy) of 10.9%. Conclusion: An excellent rate of tumor control was observed in this prospective trial. By using multiple assessment techniques, we are showing acceptable cosmesis, supporting the use of IMRT planned APBR with daily schedule in elderly patients with early stage BC.

Radiopharmaceuticals for the Therapy of Metastatic Bone Pain (뼈전이의 방사성동위원소 통증치료)

  • Ahn, Byeong-Cheol
    • Nuclear Medicine and Molecular Imaging
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    • v.40 no.2
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    • pp.82-89
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    • 2006
  • Bone metastasis is a common sequelae of solid malignant tumors such as prostate, breast, lung, and renal cancers, which can lead to various complications, including fractures, hypercalcemia, and bone pain, as well as reduced performance status and quality of life it occurs as a result of a complex pathophysiologic process between host and tumor cells leading to cellular invasion, migration adhesion, and stimulation of osteoclastic and osteoblastic activity. Several sequelae occur as a result of osseous metastases and resulting bone pain can lead to significant debilitation. A multidisciplinary approach is usually required not only to address the etiology of the pain and its complicating factors but also to treat the patient appropriately. Pharmaceutical therapy of bone pain, includes non-steroidal analgesics, opiates, steroids, hormones, bisphosphonates, and chemotherapy. While external beam radiation therapy remains the mainstay of pain palliation of a solitary lesions, bone seeking radiopharmaceuticals have entered the therapeutic armamentarium for the treatment of multiple painful osseous lesions. $^{32}P,\;^{89}SrCl,\;^{153}Sm-EDTMP,\;^{188}Re/^{186}Re-HEDP,\;and\;^{177}Lu-EDTMP$ can be used to treat painful osseous metastases. These various radiopharmaceuticals have shown good efficacy in relieving bone pain secondary to bone metastasis. This systemic form of metabolic radiotherapy is simple to administer and complements other treatment options. This has been associated with improved mobility in many patients, reduced dependence on narcotic and non-narcotic analgesics, improved performance status and quality of life, and, in some studios, improved survival. All of these agents, although comprising different physical and chemical characteristics, offer certain advantages in that they are simple to administer, are well tolerated by the patient if used appropriately, and can be used alone or in combination with the other forms of treatment. This article illustrates the salient features of these radiopharmaceuticals, including the usual therapuetic dose, method of administration, and indications for use and also describe about the pre-management checklists, and jndication/contraindication and follow-up protocol.

Recent Trend in Bioscavengers for Inactivation of Toxic Organophosphorus Compounds (유기인 계열 독성물질 분해를 위한 바이오스캐빈저 최신 연구 동향)

  • Kim, Heejeong;Jeong, Keunhong;Kye, Young-Sik
    • Applied Chemistry for Engineering
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    • v.31 no.2
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    • pp.125-137
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    • 2020
  • In recent years, toxic organophosphorus compounds (OPs) have been used for civilians, becoming a great threat to the world. Alternative to the current treatment policy unpredictable for any prevention, researches on bioscavenger as an improved treatment have been actively conducted. Bioscavengers refer to proteins and enzymes that prevent intoxication by inactivating or binding toxic OPs before they reaches the target. In particular, extensive efforts have been made to develop catalytic bioscavengers that quickly detoxify OPs even with a small dose of the protein by performing multiple binding and hydrolysis processes with OPs. This review introduces the latest studies and results for developing catalytic bioscavengers using molecular evolution and protein engineering techniques. We will briefly present some of the remaining challenges on developing enzymes into clinically approved drugs.

Initial Experiences of Extracorporeal Membrane Oxygenation for Trauma Patients at a Single Regional Trauma Center in South Korea

  • Ko, Ji Wool;Park, Il Hwan;Byun, Chun Sung;Jang, Sung Woo;Jun, Pil Young
    • Journal of Trauma and Injury
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    • v.34 no.3
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    • pp.162-169
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    • 2021
  • Purpose: For severe lung injuries or acute respiratory distress syndrome that occurs during critical care due to trauma, extracorporeal membrane oxygenation (ECMO) may be used as a salvage treatment. This study aimed to describe the experiences at a single center with the use of ECMO in trauma patients. Methods: We enrolled a total of 25 trauma patients who were treated with ECMO between January 2015 and December 2019 at a regional trauma center. We analyzed and compared patients' characteristics between survivors and non-survivors through a medical chart review. We also compared the characteristics of patients between direct and indirect lung injury groups. Results: The mean age of the 25 patients was 45.9±19.5 years, and 19 patients (76.0%) were male. The mean Injury Severity Score was 26.1±10.1. Ten patients (40.0%) had an Abbreviated Injury Scale (AIS) 3 score of 4, and six patients (24.0%) had an AIS 3 score of 5. There were 19 cases (76.6%) of direct lung injury. The mortality rate was 60.0% (n=15). Sixteen patients (64.0%) received a loading dose of heparin for the initiation of ECMO. There was no significant difference in heparin use between the survivors and non-survivors (70% in survivors vs. 60% in non-survivors, p=0.691). When comparing the direct and indirect lung injury groups, there were no significant differences in variables other than age and ECMO onset time. Conclusions: If more evidence is gathered, risk factors and indications will be identified and we expect that more trauma patients will receive appropriate treatment with ECMO.

Effect of Yeonsan Ogye bioactive peptides on anti-oxidant indexes in rats' liver

  • Kim, Hye Won;Shim, Jung Hun;Kim, Ki Nam
    • Journal of Nutrition and Health
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    • v.52 no.4
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    • pp.408-411
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    • 2019
  • Purpose: This study investigated the effect of bioactive Yeonsan Ogye peptides (YOPs) intake on changes in the hepatic anti-oxidant indexes in male rats. Methods: Sprague-Dawley male rats were divided into 3 groups and given a casein-based AIN-93G diet and distilled water ad libitum without any added YOPs (control), distilled water with 250 mg of YOPs (Y250), or 500 mg of YOPs (Y500) per kg of body weight for 4 weeks. YOP dose was decided as referred to in the referenced study where toxicity did not occur. The hepatic anti-oxidant indexes were determined using a commercial kit. Statistical analysis was performed using SPSS version 23.0 and are expressed as $mean{\pm}standard$ error of mean. Differences among the groups were evaluated by one-way analysis of variance followed by post hoc Duncan's multiple comparisons test. Results: There were no differences in the body weights, weight gain, food intake, food efficiency ratio, or organ weight, including liver, kidney, spleen, thymus, and epididymal fat, among all of the groups. The hepatic nitric oxide (NO) level in the Y500 group was lower than that in the control and Y250 groups, and the hepatic malondialdehyde (MDA) level was lower in the Y500 group than in the Y250 group. The differences in hepatic superoxide dismutase (SOD) and catalase (CAT) activities were not statistically significant between the groups. From these results we speculated that YOPs may have anti-oxidative abilities to regulate NO and MDA production without affecting SOD and CAT activities. Conclusion: YOPs are presumed to act as anti-oxidants in the animal or human body.