• 제목/요약/키워드: First-In-Man dose

검색결과 48건 처리시간 0.019초

Calculation of a First-In-Man Dose of 7-O-Succinyl Macrolactin A Based on Allometric Scaling of Data from Mice, Rats, and Dogs

  • Noh, Keumhan;Kang, Wonku
    • 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.

상구암종의 외과적 치료 -2례 보고- (Surgical Management of Pancoast Tumor -2 Cases Report-)

  • 안정태
    • Journal of Chest Surgery
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    • 제28권4호
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    • pp.426-430
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    • 1995
  • Pancoast tumor was specific lung carcinoma that has been symptoms and signs according to locations. It was located in peripheral,and involved the extrathoracic structures more than parenchyme of the lung. At 1838, Hare reported it, and at 1932 Pancoast was first described it. Prior to 1950,superior sulcus tumor was considered uniformly fatal, but at 1961 Paulson and Shaw advocated the use of preoperative irradiation therapy and followed by an extended en bloc resection. Recently we were experienced 2 cases of pancoast tumor managed with same method. One was 60-years old man that has been recommended preoperative radiation therapy with dose of 3000 cGy to 20 fractions and followed resection after 4 weeks, the other was 53-years old man that has been recommended a dose of 4000 cGy to 20 fractions and followed resection after 4 weeks. On tumor histology first case was large cell carcinoma and second case was squamous cell carcinoma. all patients was complicated atelectasis. First patient was expired with brain metastasis after 17 months, second was expired after 6 months.

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Radiation Exposure from Nuclear Power Plants in Korea: 2011-2015

  • Lim, Young Khi
    • Journal of Radiation Protection and Research
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    • 제42권4호
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    • pp.222-228
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    • 2017
  • Background: On June 18, 2017, Korea's first commercial nuclear reactor, the Kori Nuclear Power Plant No. 1, was permanently suspended, and the capacity of nuclear power generation facilities will be adjusted according to the governments denuclearization policy. In these circumstances, it is necessary to assess the quality of radiation safety management in nuclear power plants in Korea by evaluating the radiation dose associated with them. Materials and Methods: The average annual radiation dose per unit, the annual radiation dose per person, and the annual dose distribution were analyzed using the radiation dose database of nuclear reactors for the last 5 years. The results of our analysis were compared to the specifications of the Nuclear Safety Act and Medical Law in Korea. Results and Discussion: The annual average per unit radiation dose of global major nuclear power generation was 720 man-mSv, while that of Korea's nuclear power plants was 374 manmSv. No workers exceeded 50 mSv per year or 100 mSv in 5 years. The individual radiation dose according to occupational exposure was 0.59 mSv for nuclear workers, 1.77 mSv for non-destructive workers, and 0.8 mSv for diagnostic radiologists. Conclusion: The radiation safety management of nuclear power plants in Korea has achieved the best outcomes worldwide, which is considered to be the result of the as-low-as-reasonably-achievable (ALARA) approach and strict radiation safety management. Moreover, the occupational exposures were also very low.

사춘기 암컷 랫드에서 갑상선 시험에 의한 Methoxychlor의 에스트로젠 효과 (The Estrogenic Effects of Methoxychlor in Pubertal Female Rats: Establishment of Thyroid Assay for Endocrine Disruptors)

  • 정문구;김종춘;임광현
    • Toxicological Research
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    • 제16권1호
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    • pp.27-31
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    • 2000
  • Recently, there is a worldwide concern that a great number of man-made chemicals have a hormone-like action both in humans and in animals. EPA and OECD are developing screening programs using validated test systems to determine whether certain substances may have an effect on humans. In the present study, the establishment of in vivo short-term test system for pubertal female assay with thyroid to detect endocrine disrupting chemicals was tried using a model substance, methoxychlor (MC), a chlorinated hydrocarbon insencticide. Forty female rats were assigned to four groups. MC was administered at dose levels of 0, 8, 40 and 200mg/kg by gavage to female rats from day 21 post partum to the completion of vaginal opening. We evaluated body weight change, age at vaginal opening, onset of estrous cyclicity, age at first esturs, ovary weight, and serum concentrations of thyroxine and thyroid stimulating hormone in female rats. The age at vaginal opening of females receiving 40 200mg/kg was significantly younger than control. The onset of estrus cyclicity and age at first estrus of females receiving 200mg/kg was also younger than controls. There was no effect of treatment on body weight, ovary weight, and hormone concentration. Based on these results, it can be concluded that application of MC at dose level of 40mg/kg affects the vaginal opening and application of MC at dose level of 200mg/kg accelerates the vaginal opening and the onset of estrus cylicity.

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The Effects of Panax ginseng and P. quinquefolium on Hemodynamics and Body Temperature in Healthy Young Men (III)

  • Lee, Jee-Hwan;Cho, Jung-Ah;Ki, Chan-Young;Son, Yeon-Kyoung;Park, Jeong-Hill;Park, Man-Ki;Han, Yong-Nam
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
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    • pp.108-108
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    • 2003
  • The current study was performed to observe the effects of Panax ginseng (PG) and P. quinquefolia (PQ) on hemodynamics such as blood flow rate (BF), blood flow velocity (BV), heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP, and body temperature (BT) in healthy young men. After testing equality of variance, Student's t-test using PROC TTEST was examined to. prove statistical differences between control and ginseng conditions at each time point. It was found that the BF data were fluctuated by personal deviation. In order to minimize the deviation, the results obtained for 6 hrs were reconstituted after dividing them into two periods of the first half from 1 to 3 hrs and of the latter half from 3.5 to 6 hrs. And then the reconstitution data and dose-response curves were obtained. Blood flow such as BF and BV shows significant increases both two periods in the dose of PG 2.25 and PG 9.0, whereas significant decrease in the dose of PG 4.5. However, in the PQ groups, the middle dose PQ 4.5 shows the highest significant increase among the three doses. Except for PG 2.25 in HR, other doses show significant decreases both in the first half and latter half. SBP of PQ 9.0 shows only a significant decrease in the first half; on the other hand, in the latter half, PG 4.5, PG 9.0 and PQ 9.0 significantly increase SBP. In addition, DBP of PG 2.25 and PG 4.5 show significant increase in the both periods. In the BT, PQ groups show gradual decrease from PQ 2.25 to PQ 9.0; however, PG groups show differently. PG 4.5 shows significant decrease, but PG 9.0 shows a increase without statistical meanings. In summary, PG is more effective in respect to keeping homeostasis of hemodynamics.

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CHANGING OF RGS TRANSCRIPTS LEVELS BY LOW-DOSE-RATE IONIZING RADIATION IN MOUSE TESTIS

  • Kim, Tae-Hwan;Baik, Ji Sue;Heo, Kyu;Kim, Joong Sun;Lee, Ki Ja;Rhee, Man Hee;Kim, Sung Dae
    • Journal of Radiation Protection and Research
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    • 제40권3호
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    • pp.187-193
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    • 2015
  • Deleterious effects of high dose radiation exposure with high-dose-rate are unarguable, but they are still controversial in low-dose-rate. The regulator of G-protein signaling (RGS) is a negative regulator of G protein-coupled receptor (GPCR) signaling. In addition, it is reported that irradiation stress led to GPCR-mediated mitogen-activated protein kinase (MAPK) and phosphotidylinositol 3-kinase (PI3-k) signaling. The RGS mRNA expression profiles by whole body radiation with low-dose-rate has not yet been explored. In the present study, we, therefore, examined which RGS was modulated by the whole body radiation with low-dose-rate ($3.49mGy{\cdot}h^{-1}$). Among 16 RGS expression tested, RGS6, RGS13 and RGS16 mRNA were down-regulated by low-dose-rate irradiation. This is the first report that whole body radiation with low-dose-rate can modulate the different RGS expression levels. These results are expected to reveal the potential target and/or the biomarker proteins associated with male testis toxicity induced by low-dose-rate irradiation, which might contribute to understanding the mechanism beyond the testis toxicity.

경주 중·저준위방사성폐기물 처분시설의 방폐물검사건물에서 해체 방사성폐기물 대상 방사선작업종사자의 피폭선량 평가 및 작업조건 도출 (The Assessment of Exposure Dose of Radiation Workers for Decommissioning Waste in the Radioactive Waste Inspection Building of Low and Intermediate-Level Radioactive Waste Disposal Facility)

  • 김린아;도호석;김태만;조천형
    • 방사성폐기물학회지
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    • 제18권2_spc호
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    • pp.317-325
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    • 2020
  • 한국원자력환경공단은 처분시설 내 1단계 인수·저장구역의 인수검사 공간 및 드럼 취급 공간 부족에 대한 문제를 해결하기 위하여 방폐물검사건물을 건설하여 저장·처리능력을 확충할 예정이다. 본 연구에서는 MCNP 코드를 이용하여 방폐물검사건물 내 저장구역에서 취급하는 해체 방사성폐기물 대상 신형처분용기를 대상으로 작업종사자의 피폭선량을 평가하였다. 평가결과, 시설 내 저장 가능한 최대 용기 개수(304개)와 방사선작업에 대한 연간 예상 작업시간(약 306시간)에 대하여 연간 집단선량은 총 84.8 man-mSv로 계산되었다. 시설 내 총 304개의 신형처분용기(소형/중형 타입)가 저장 완료된 시점에서 인수검사, 처분검사를 위한 작업종사자의 투입인력은 총 25명, 작업종사자 당 예상피폭선량은 연평균 3.39 mSv로 산출되었다. 소형용기 취급 시 작업종사자의 고방사선량 작업에 따른 작업효율과 방사선적 안전성 확보를 위해서는 콘크리트 라이너의 두께를 증가시키는 추가적인 차폐가 필요할 것으로 평가되었다. 향후 본 연구를 바탕으로 실측기반의 해체폐기물의 선원항과 특성을 활용하여 방사선작업 당 작업시간 및 투입인력을 산출함으로써 작업종사자의 최적의 방사선작업조건을 도출할 수 있을 것으로 사료된다.

운동유발성 기관지수축의 정도와 Methacholine 유발시험의 민감도 및 최대기도협착과의 관련성 (Correlation of Exercise-Induced Bronchoconstriction to $PC_{20}$ and Maximal Airway Narrowing on the Dose-Response Curve to Methacholine)

  • 임형석;윤경애;고영률
    • Tuberculosis and Respiratory Diseases
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    • 제42권2호
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    • pp.165-174
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    • 1995
  • 연구배경: 운동유발성 천식은 운동에 의해서 기관지 수축이 나타나는 것으로, 일상생활에서 흔히 경험하는 천식발작의 형태로서, 특히 소아에서는 중요하다. 이러한 운동유발성 기관지 수축은 비특이적으로 발생된다는 점에서, 통상적으로 측정, 평가되는 histamine이나 metacholine에 의한 비특이적 기관지 반응도와 밀접한 관련을 생각할 수 있다. 비특이적 기관지 반응도 중 $PC_{20}$으로 표시되는 기도 민감도는 운동유발성 기관지 수축의 정도와 비례하는 것이 밝혀져 있으나, 또 다른 요소인 최대 기도 협착의 정도와 운동유발성 기관지 수축(EIB)의 정도와의 연관성에 대해서는 연구된 바 없다. 방법: 56명의 천식 환아에서 고농도의 methacholine 유발시험에서의 $PC_{20}$, 최대반응고원(MRP), 최대기도 협착(MAN)을 측정하고, 운동유발시험에서의 운동유발성 기관지수축을 측정하였다. 이들을 운동유발성 기관지 수축의 정도에 따라 3군으로 구분하여, 각군간의 $PC_{20}$, MRP, MAN의 차이를 알아보고 전체 대상에서 운동유발성 기관지 수축의 정도와 $PC_{20}$, MRP, MAN 각각과의 상관관계를 알아보았다. 결과: 1) 운동유발성 기관지 수축이 20% 이상인(+) EIB군의 $PC_{20}$은, 10% 이하인 (-)EIB의 $PC_{20}$보다 유의하게 낮았다(p<0.01). 2) 전체 대상에서 methacholine $PC_{20}$의 log치는 운동유발성 기관지수축의 정도와 유의한 역비례 관계를 나타내었다(r=-0.568, p<0.01). 3) 전체 56명중 36명에서 MRP를 구할수 있었는데 이들에서 MRP와 운동유발성 기관지 수축의 정도는 유의한 상관관계를 보였다(r=0.355, p<0.05). 4) (+)EIB인 군의 MAN은 (-)EIB군의 MAN보다 유의하게 높았다. 5) 전체 대상에서 MAN은 운동유발성 기관지 수축의 정도와 유의한 정비례 관계를 나타내었다(r=0.546, p<0.01). 결론: 운동유발성 기관지 수축의 정도는 methacholine유발검사로 측정된 $PC_{20}$과 뿐만 아니라 MAN의 정도와 유의한 상관관계를 나타내었다. 이같은 결과는 비록 특이적 기관지 반응도를 결정하는 2가지 요소가, 비록 서로 다른 기전이지만, 운동에 대한 반응을 결정하는 요인으로 중요하게 작용함을 암시한다. 또한 NSBR을 평가할때 $PC_{20}$뿐만 아니라 MRP혹은 MAN의 측정이 가능한 포함되어야 할것이다.

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거미낭으로 일과성 정신병 유발이 의심되고 리스페리돈 치료에 효과적이었던 증례 (A Case of Transient Psychosis Suspected to be Induced by Arachnoid Cyst, Which was Responsive to Risperidone)

  • 박원명;배치운;전태연;김광수;유태열
    • 생물정신의학
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    • 제8권1호
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    • pp.153-155
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    • 2001
  • There had been few reports of arachnoid cyst accompanying psychiatric disturbance and no report treated with low-dose risperidone administration. We report a patient, developed first-transient psychotic episode considered to be provoked by an arachnoid cyst, responsive to risperidone, which was found in the middle cranial fossa as follows. A 57-year-old man was admitted by suddenly developed headache, auditory hallucination, delusion of persecution and, an arachnoid cyst in the anteromedial aspect of middle cranial fossa was found on MRI after admission. The psychotic episode was first to him and he was also negative to other clinical evaluation including endocrine abnormality, his psychotic symtom was suspected to be induced by arachnoid cyst and was well controlled to low-dose risperidone administration. He left hospital free from psychotic symptoms on 14 hospital days.

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자발성 뇌내혈종의 음압배액술 (Negative Pressure Aspiration of Spontaneous Intracerebral Hematoma)

  • 김일만;손은익;김동원;임만빈
    • Journal of Korean Neurosurgical Society
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    • 제29권6호
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    • pp.738-743
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    • 2000
  • Objectives : The less invasive stereotactic surgery of hypertensive intracerebral hematoma has been preferred. Many techniques were developed to facilitate aspiration of a dense blood clot in acute stage. Authors describe a method for evacuation of putaminal hematoma via computerized tomography(CT)-aided free-hand stereotactic infusion of urokinase and frequent negative pressure aspiration. Patients and Methods : A total of ten patients with spontaneous putaminal hematoma underwent surgery with negative pressure aspiration in the three-year period. All procedures were performed within 12 hours of insult. A silicone ventricular catheter was inserted into the center of hematoma through a burr hole at the Kocher's point under local anesthesia. In a typical case of putaminal hematoma, the trajectory of catheter was pointed the center of hematoma parallel to sagittal plane vertically and the external auditory meatus posteriorly. Immediately after the first trial of hematoma aspiration low-dose urokinase solution(2,000IU/5ml saline) was administrated through the catheter and drain was clipped for 30 minutes. Subsequently, the partially liquified hematoma was manually aspirated using a 10ml syringe with a negative pressure of less than 2 to 3ml. The procedure was carefully repeated every 1 hour until the hematoma was near totally evacuated. Results : The patients population consisted composed of 4 men and 6 women with a mean age of 61.6 years. All had major neurological deficits preoperatively. The mean hematoma volume was 44.3 ml and hematoma was drained for 20 to 48 hours. No complications such as rebleeding, meningitis, or malplaced catheter were noted. Outcome was moderately disabled in four patients and good recovery in three patients. Conclusion : Although the frequent negative pressure aspiration and low-dose urokinase infusion has the disadvantage of possbility of rebleeding and infection, it is consisdered to be an effective method because it allows a simple, safe, and complete removal of hematoma.

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