• Biomolecules & Therapeutics
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• 제2권2호
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• pp.190-205
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• 1994

This study was conducted to investigate the repeated dose toxicity of DA-125, a new anthracycline antitumor antibiotic, in rats. Before the 13-week main study, a 4-week dose-range finding (DRF) study was carried out. The administration of DA-125 intravenously at dosage levels of 0, 0.125, 0.5, 2.0, and 8.0 mg/kg/day to rats for 4 weeks resulted in premature deaths of all animals in the 8.0 mg/kg/day group and in the deaths of 4 males and 4 females at 2.0 mg/kg/day. Body weights were markedly reduced in the 8.0 mg/kg/day group and showed dose-related decreases in all treatment groups when compared with the control group. Reductions in weight gain were slight and not significantly different at 0.125 mg/kg/day but animals receiving 0.5 mg/kg/day showed more marked decreases in gain in a clear dose-related manner Based On the results of the above DRF study, a 13-week repeated dose intravenous toxicity study in rats with DA-125 was performed at a dose level of 0, 0.012, 0.08 and 0.3 mg/kg/day. No treatment related effects were noted in behavior or body weight in all treatment groups. One male at the highest dose level died on study day 26, but the death could not be related to test article toxicity. Swelling and scabbing of the ears was present in all of the groups, including the control group. There were no treatment related changes in the hematological, biochemical or urinalysis values in all treatment groups. Thymus weights were significantly reduced ill males receiving 0.3 mg/kg/day and they were sligltly, and not significantly, reduced in females of the same group. While there were no associated histological changes. Treatment related necrosis was found in the tail vein (injection site) at 0.08 and 0.3 mg/kg/day. On the basis of these results, the no observed effect level (NOEL) was 0.012 mg/kg/day and the maximum tolerated dose (MTD) was estimated to be more than 0.3 mg/kg/day under the conditions tested.

• Clinical and Experimental Reproductive Medicine
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• 제16권2호
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• pp.205-210
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• 1989

To investigate the effects of ovarian cysts on the controlled ovarian hyper-stimulation cycles, 16 patients with 16 paired cycles for IVF-ET were analyzed. These patients had taken both type of cycles, i.e., with cyst(cyst group) and without cyst(control group). Mean diameter of ovarian cysts in cyst group was 18.2mm. There were no significant differences in hormone levels in early follicular phase between two groups. No significant differences were found in total dosage of hMG(IU) administered during the ovarian stimulation $843.8{\pm}123.0$ vs $891.0{\pm}129.8$, serum estradiol level (pg/ml) on the day of hCG administration($1542.8{\pm}1100.6$ vs $1567.5{\pm}1193.0$), the number of aspirated follicles $10.0{\pm}3.4$ vs $11.2{\pm}4.3$ and oocytes $5.3{\pm}3.3$ vs $6.2{\pm}3.1$, the fertilization rate(51.2 % vs 57.2 %) and the cleavage rate(40.5 % vs 52.0 %). Serum estradiol terminal patterns during COH in one group tended to be repeated in the other group. In conclusion, this study suggests that small ovarian cysts do not adversely impact on the controlled ovarian hyperstimulation parameters in IVF - ET program and the presence of small ovarian cyst without concomitant high basal serum estradiol level is not an indication of the cancellation of the controlled ovarian hyperstimulation for IVF-ET.

• 한국임상약학회지
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• 제6권2호
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• pp.19-23
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• 1996

Carbamazepine is an anticonvulsant drug that has been shown to be as effective as phenytoin or phenobarbital in treatment of grand mal and complex partial seizures and is also approved as the drug of choice for treatment of the pain associated with trigerminal neuralgia. And the therapeutic or toxic effects of carbamazepine are better related to plasma concentration than to dosage, which can be attributed to interindividual variability in the pharmacokinetics. A slow rate of carbamazepine dissolution in the gastrointestinal tract is believed to be the cause of its relatively slow and erratic rate of absorption. For these reasons pharmacokinetic evaluation of newly formulated carbamazepine is neccessary. In this study, the bioequivalence in carbamazepine between the $TegretoI^{TM}$ CR tablet (Geigy Co.) and $Carmazepine^{TM}$ CR tablet (Myung In Co.) was evaluated. 12 normal volunteers (age $21\~27$ years old) was divided into two groups, and a randomized cross-over study was employed. The pharmacokinetic parameters ($C_{max},\;T_{max}$ and AUC) obtained of oral administration of each formulatim of carbamazepine 400 mg were evaluated and ANOVA was utilized for the statistical analysis of parameters. $C_{max}\;is\;8.26{\pm}3.1{\mu}g/ml\;(C.V.\;37.3\%)\;in\;TegretoI^{TM}\;and\;9.39\{pm}2.9{\mu}g/ml\;(C.V.\;30.5\%)$ in $Carmazepine^{TM},\;T_{max}\;is\;28.0{\pm}5.9\;hrs(C.V.\;21.1\%)$ in $Tegretol^{TM}\;and\;24.0{\pm}7.2\;hrs(C.V.\;30.2\%)$ in $Carmazepine^{TM}$ and AUC is $786.4{\pm}360.5{\mu}g{\cdot}hr/ml\;(C.V.\;45.8\%)$ in $TegretoI^{TM}\;and\;792.8{\pm}228.6{\mu}g{\cdot}hr/ml\;(C.V.\;28.8\%)$ in $Carmazepine^{TM}$, respectively. As the result of the data, two formulations are bioequvalent, and the lower C.V. of $Carmazepine^{TM}$ in every individual can be merit.

• 동의생리병리학회지
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• 제25권4호
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• pp.650-657
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• 2011

The object of this study was to obtain acute information (single oral dose toxicity) of Taraxaci Herba (Dried total parts of Taraxacum platycarpum. H.Dahlstedt (Compositae)), has been traditionally used in Korean medicine for treating various inflammatory diseases. In order to observe the 50% lethal dose (LD 50), approximate lethal dosage (ALD) and target organs, test articles were once orally administered to female and male ICR mice at dose levels of 2,000, 1,000, 500 mg/kg according to the recommendation of Korea Food and Drug Administration Guidelines. The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after single oral treatment of Taraxaci Herba aqueous extracts according to KFDA Guidelines with organ weights and histopathological observations of 12 types of principle organs. After single oral treatment of Taraxaci Herba aqueous extracts, we could not find any mortality and toxicological evidences up to 2,000 mg/kg treated group, the limited dosages in rodents at body and organ weights, clinical signs, gross and histopathological observations. Except for slight soft feces, which were detected in male mice treated with 2,000 mg/kg of Taraxaci Herba aqueous extracts at 1 day after end of treatment. The results obtained in this study suggest that the LD 50 and ALD of Taraxaci Herba aqueous extracts in both female and male mice after single oral treatment were considered as over 2,000 mg/kg because no mortalities were detected up to 2000 mg/kg that was the highest dose recommended by KFDA and OECD. However, it also observed that the possibility of digestive disorders, like diarrhea when administered over 2,000 mg/kg of Taraxaci Herba aqueous extracts in the present study, but these possibilities of digestive disorders can be disregard in clinical use because they ate transient in the highest dosages male only.

• 한국환경과학회지
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• 제31권8호
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• pp.677-689
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• 2022

In order to photocatalytically treat organic matter (COD_Cr) and chromaticity effectively, chemical coagulation and sedimentation processes were employed as a pretreatment of the leachate produced from landfill in Jeju Island. This was performed using FeCl₃·6H₂O as a coagulant. For the treated leachate, UV/TiO₂ and UV/TiO₂/H₂O₂ systems were investigated, using 4 types of UV lamps, including an ozone lamp (24 W), TiO₂ as a photocatalyst, and/or H₂O₂ as an initiator or inhibitor for photocatalytic degradation. In the chemical coagulation and sedimentation process using FeCl₃·6H₂O, optimum removal was achieved with an initial pH of 6, and a coagulant dosage of 2.0 g/L, culminating in the removal of 40% COD_Cr and 81% chromaticity. For the UV/TiO₂ system utilizing an ozone lamp and 3 g/L of TiO₂, the optimum condition was obtained at pH 5. However, the treated COD_Cr and chromaticity did not meet the emission standards (COD_Cr: 400 mg/L, chromaticity: 200 degrees) in a clean area. However, for a UV/TiO₂/H₂O₂ system using 1.54 g/L of H₂O₂ in addition to the above optimum UV/TiO₂ system, the results were 395 mg/L and 160 degrees, respectively, which were within the emission standard limits. The effect of the UV lamp on the removal of COD_Cr, and chromaticity of the leachate decreased in the order of ozone (24 W) lamp > 254 nm (24 W) lamp > ozone (14 W) lamp > 254 nm (14 W) lamp. Only COD_Cr and chromaticity treated with the ozone (24 W) lamp met the emission standards.

• 대한예방한의학회지
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• 제19권3호
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• pp.91-102
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• 2015

Objective : The purpose of this study is to find out the possibility of application to herbal medicine's report form for adverse drug reaction (ADR) by reviewing and analyzing Asian countries's ADR report forms. Method : We investigated, compared, and analyzed ADR report forms (ADR-RF) of Asian countries's ADR institutions (ACAI), such as, Korea institute of drug safety & risk management and Dongguk university Ilsan oriental hospital (DUIOH) in Korea, national center for ADR monintoring (NCAM) in China, pharmaceuticals and medical devices agency (PMDA) in Japan, Ministry of Health and Welfare (MOHW) in Taiwan, and drug office, department of health, the government of the Hong Kong special administrative region (GHKSAR) in Hong Kong. Results : ADR-RF for ACAI included common contents, such as, patients information (name(initial), gender, age, weight), adverse event (AE)'s report information (Recognition and report for AE occurrence, first or follow up report, Severe AE), the detailed information of AE (the title of AE, onset & closing date of AE symptoms, the progress & results detailed test of AE), the information of AE's medicine (the types of medicine, product name, ingredient name, suspected or combination drug, single dose & frequency, dosage form, administration route, dealing for AE-suspected medicine), and AE reporter's information (reporter's information, institution's information). Taiwan had ADR-RF and the department exclusively for herbal medicine (HM), but others (except DUIOH) had not only no ADR report form but also contents for HM. Conclusion : ADR-RF for HM have to include the common contents of ACAI at least, as well as HM information related to ADR, such as the title, composition and types of HM, history related to HM's ADR, and the contents of drug-induced liver injury and so on. In addition, the main department of government for HM's ADR will be needed.

• Journal of Applied Biological Chemistry
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• 제60권3호
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• pp.227-234
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• 2017

염증성 장 질환에 일반적으로 사용되는 설파살라진은 고용량 및 장기 섭취 후 다양한 부작용이 있다. 본 연구에서는 TNBS로 유발된 마우스 대장염 모델에서 설파살라진, 육계와 시호 복합 추출물의 항염증 및 세포 자멸 개선효과를 확인하고자 하였다. 실험은 정상군, TNBS 대조군, Sulfasalazine (30 mg/kg)군, Sulfasalazine (60 mg/kg)군, Sulfasalazine (30 mg/kg)+육계 및 시호 혼합 (30 mg/kg)군, 총 5개의 군으로 나누었으며, 7일간 경구투여 하였다. 염증 및 세포 자멸 단백질은 western blot을 통해 발현량을 확인하였다. SCB 투여는 염증 단백질 및 세포 자멸과 관련된 단백질의 억제에 유의한 효과를 나타냈다. 이러한 결과로 보아 설파살라진, 육계와 시호 복합 추출물은 염증과 세포 자멸의 억제를 통해 염증성 장 질환을 개선시킬 수 있으며, 염증성 장 질환의 치료 대안 가능 물질로 사료되는 바이다.

• Toxicological Research
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• 제14권3호
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• pp.435-441
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• 1998

Alginase$Alginase^{ⓡ}$ (Arginine esterase) is one of the snake venoms which is mainly consisted of arginine esterase and acts as a thrombus -forming inhibitor/thrombus-lysin. These present studies were performed to investigate of the acute and subacute toxicity of the Alginase$Alginase^{ⓡ}$ in rats. In acute toxicity study, rats were single administered intravenously with dosages of 0.001, 0.01. 0.1, 1 and 10U/kg B.W. and examined the number of death, clinical sign, body weight and pathological change for 7days after administration of Alginase$Alginase^{ⓡ}$. At maximum dose level (10U/kg B.W.), Alginase$Alginase^{ⓡ}$ induced symptoms of shock with cyanosis and dyspnea. But these symptoms dissappeared after 30~50 minutes and we could not find any other toxic effect in rats. Therefore, $LD_{50}$ Value of Alginase was over 10U/kg B.W. in rats. In four-week intravenous toxicity study of Alginase$Alginase^{ⓡ}$, rats were administered intravenously seven days per week for 28 days, with dosages of 0, 0.0125, 0.125 and 1.25U/kg B.W./day, respectively. Alginase$Alginase^{ⓡ}$ did not caused any death and showed any clinical signs in rats. No significant Alginase$Alginase^{ⓡ}$ -related changes were found in feed uptake, water consumption, hematology, serum biochemistry, urinalysis, ocular examination, organ weight and histopathological examination. From the results, Alginase$Alginase^{ⓡ}$ seems not to have any toxic effect in rats when it were given daily intravenous injections below the dosage 1.25U/kg B.W./day for four weeks.

• 약학회지
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• 제44권3호
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• pp.224-231
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• 2000

$Nokyangbotang^{TM}$ (NYBT) is a kind of powerful food for health and have been drunk at a oral dose of 80 ml (99.5 mg) three times per day: It has not been well studied about the anti-fatigue and hepatoprotective activity. In this experiments, we evaluated pathophysiologically the effect of NYBT on swimming time in mouse and hepatoprotective activity in rats intoxicated with carbon-tetrachloride. NYBT was nontoxic in orally acute toxicity test ($LD_{50}$, 320 ml/60 kg): a nontoxic food in more four times of one-shoot dosage (80 ml) to human. Weight-loaded forced swimming test was carried out to measure the swimming time of mice with a 4% load of body weight in plastic cylinder (diameter $10{\;}cm{\;}{\times}{\;}height{\;}20{\;}cm$) on water bath at $25^{\circ}C$, and the anti-fatigue activity represented the ratio of swimming time of experimental group to that of control group. NYBT had dose-dependent anti-fatigue activity Mice administered NYBT at a dose of 320 ml/60 kg once daily for 5 days could swim about two times more than control. Hepatoprotective activities of NYBT were examined by the determination of malonedialdehyde (MDA) and pathological survey in liver and liver function test of rat intoxicated with $CCl_4$ at i.m. dose of 2 ml/kg once daily for 7days. NYBT decreased dose-dependently thiobarbituric acid reactive substance: Oral administration of NYBT at a dose of 20 ml/60 kg was $38.51{\;}{\pm}{\;}3.02$ nmol MDA/g of tissue, that of 80 ml/60 kg was $33.76{\;}{\pm}{\;} 1.84$ nmol MDA/g of tissue, and that of 320 ml/60 kg was $32.87{\;}{\pm}{\;}1.90$ nmol MDA/g of tissue as compared with control group ($43.61{\;}{\pm}{\;}2.85$ nmol MDA/g of tissue). All rats administered NYBT at a dose of 320 ml/60 kg were survival as compared with 40% survival of control animals, and GPT activity of rats administered NYBT at a dose of 80 ml/60 kg was decreased as compared with control. In histopathological survey, NYBT improved slightly the fatty changes of hepatocytes around centrilobular area. These results suggest that NYBT has anti-fatigue and hepatoprotective activity in rats and mice.

• 한국임상약학회지
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• 제27권2호
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• pp.92-98
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• 2017

Background: Nebulized colistimethate is increasingly used, because there are problems such as renal dysfunction and low distribution within the lungs when colistimethate is administered intravenously. This study was designed to compare and analyze the changes in renal function by of nebulized colistimethate treatment for its safe administration. Methods: This study retrospectively reviewed the electronic medical records of adult patients above 19 years old, receiving only the nebulized colistimethate at least 4 days in Yonsei university health system from Nov 2014 to Aug 2015. Acute kidney injury (AKI) was determined by using the RIFLE criteria (Risk, Injury, Failure, Loss and End-stage renal disease) according to serum creatinine (SCr) levels before and after use of nebulized colistimethate. Results: 48 patients were included our study and their SCr increased significantly after nebulized colistimethate treatment ($SCr_0$ vs. $SCr_1$; $0.85{\pm}0.80$ vs. $1.00{\pm}0.82mg/dL$, n=48, p<0.001), but the changes were in normal range according to the standards at Yonsei university health $system^a$. Among 48 patients, 38 patients were in the non-AKI group (79.2%), and 10 patients developed AKI (20.8%). Within the AKI group, 2 patients were in the Injury group (20%) and the other 8 in the Risk group (80%). Conclusion: There was no significant difference in age, dosage and duration of treatment between AKI group and non-AKI group (p>0.05). The study has a significance in that it reviewed the safety of nebulized colistimethate only treatment to national patients, analyzing its nephrotoxicity. It has confirmed that nebulized colistimethate is a safer method than intravenous injection, and requires to establish a guideline for the use of nebulized colistimethate in further studies with broader patient groups. $^a$ : SCr Male 0.68-1.19 mg/dL, Female 0.49-0.91 mg/dL.