• 한국임상약학회지
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• 제6권2호
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• pp.7-13
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• 1996

The purposes of this study were to define the pharmacokinetic parameters of vancomycin in Korean neonates, to evaluate current neonatal vancomycin dosing guideline being used in a teaching hospital, and to develop the optimal vancomycin dosing guideline. The evaluation of 35 sets of peak and trough concentrations drawn on current dosing regimen showed that $29\%$ of peak concentrations and $46\%$ of though concentrations were within therapeutic range. Otherwise, pharmacokinetic parameters, based on 62 sets of peak and trough serum concentrations obtained from 39 neonates, showed that mean vancomycin clearance (CL), volume of distribution (Vd), and terminal elimination half-life were $0.13\pm0.08\;L/hr,\;0.94\pm0.48\;L,\;and\;5.6\pm2.13$ hours, respectively. Volume of distribution (Vd) normalized for body weight remained constant throughout PCA range, whereas the absolute CL (r=0.74) and normalized CL (r=0.36) showed high correlation with PCA. Also, the normalized CL showed a strong inverse correlation (r=-0.55) with serum creatinine concentrations (SrCr). Based on the high correlation among PCA serum creatinine concentration, CL, and the daily dosage requirements, the following dosing guideline for vancomycin in neonates was suggested: 10 mg/kg $12{\sim}18$ hourly for < 30 weeks PCA and < 0.6 mg/dl SrCr; 10 mg/kg 18 hourly for < 30 weeks PCA and $0.6{\sim}1.2$ mg/dl SrCr; 10 mg/kg 8 hourly for $30\sim44$ weeks PCA and < 0.6 mg/dl SrCr; 10 mg/kg 12 hourly for $30\sim44$ weeks PCA and $0.6{\sim}1.2$ mg/dl SrCr.

• 대한한의학방제학회지
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• 제16권1호
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• pp.147-168
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• 2008

HYTE (Hyeonggaeyeongyotang Extract), a polyherbal formula has been used as folk medicine, 28days repeat oral dose toxicity was tested in SD rats according to KFDA Guideline[2005-60]. Methods : In this study, mortality, clinical signs, body weight and gains, food and water consumption, ophthalmologic observation, urinalysis, hematology, serum biochemistry, gross findings, organ weight and histopathological observations were conducted during 28days of dosing periods. Results: 1. No HYTE treatment-related mortalities and clinical signs were detected in all dosing levels tested in male and female rats during the whole experimental periods. 2. No HYTE treatment-related changes on body weight, gains and food consumption were detected in all dosing levels tested in male and female rats during the whole experimental periods except for 2000mg/kg-dosing female groups in which significantly increase of body weight, gains, food and water consumption were detected compared to that of vehicle control in some points. 3. No HYTE treatment-related changes on ophthalmologic examination were detected in all dosing levels tested in male and female rats. 4. No HYTE treatment-related changes on urinalysis were detected in all dosing levels tested in male and female rats except for 2000mg/kg-dosing female groups in which, significantly increase of urine volume and related decrease on the urine specific gravity were detected as secondary effects of increase on the water consumptions not HYTE treatment-related toxicological signs. 5. No HYTE treatment-related changes on hematology were detected in all dosing levels tested in male and female rats except for increases in the total WBC count and lymphocytes of 2000mg/kg-dosing male and female groups with decrease of large unstained cells as pharmacological effects of immune enhancements not HYTE treatment-related toxicological signs. 6. No HYTE treatment-related changes on serum biochemistry were detected in all dosing levels tested in male and female rats. 7. No HYTE treatment-related changes on gross findings, organ weight and histopathology were detected in all dosing levels tested in male and female rats except for 2000mg/kg-dosing male and female groups in which, spleen and thymus organ weights, hypertrophy at gross observation and hyperpalsia of lymphoid cells and follicles at histopathological observation in spleen and thymus were detected as pharmacological effects of immune enhancements not HYTE treatment-related toxicological signs. Conclusions : Based on these results, the NOAEL and MTD of HYTE in SD rats were considered as over 2000mg/kg, respectively at 28days repeat oral dose toxicity test because most of these findings were considered as results of pharmacological effects of immune enhancements not HYTE treatment-related toxicological signs or secondary effects.

• 대한한방내과학회지
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• 제27권1호
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• pp.102-113
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• 2006

Objectives & Methods : To obtain the 50% lethal dose(LD50), approximated lethal dose(ALD) and approximated target organs of 'Mahwangyounpae-tang' for further study into such things as repeated dose toxicity, genotoxicity and reproductive toxicity, single dose toxicity was tested in male SD rats according to KFDA Guideline 1999-61[KFDA, 1999] at dosage levels of 2,000, 1,000, 500, 250 and 125 mg/kg/$10m{\ell}$. In this study, mortalities, clinical signs, body weight changes and body weight gains, gross findings and weight of principal organs were detected during and/or after 14 days of single dosing. Results & Conclusions : After 2 or 3 days of dosing, 1 or 2 animals in 2,000 mg/kg-dosing groups died. Excitation and leaping response were observed as test article-treatment related clinical signs. These abnormal signs were restricted to 2,000 and 1,000 mg/kg-dosing groups and survivors recovered to normal within 3 or 4 days after dosing. Significant decrease in body weight were observed in some periods of observation in 2,000 and 1,000 mg/kg-dosing group, from 1 days after dosing compared to those of vehicle control group. Significantly diminished body weight gains were observed in observation periods in 2,000 and 1,000 mg/kg-dosing group compared to those of vehicle control group. Hypertrophy and hemorrhage of heart and decoloration of kidney were observed as test article-treatment related gross findings. These abnormal findings were restricted to 2,000 and 1,000 mg/kg-dosing groups. A significant increase of absolute and relative heart and kidney weight were demonstrated in 2,000 mg/kg-dosing groups. The value for LD50 found in this study was 2,218.57 mg/kg. ALD in this study was 2,000 mg/kg, and the target organs are considered to be the heart and the kidney.

• 동의생리병리학회지
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• 제20권2호
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• pp.442-448
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• 2006

To obtain the 50% lethal dose (LD50), approximated lethal dose (ALD) and approximated target organs of 'Mahwangyounpae-tang' for further study like repeat dose toxicity, genotoxicity and reproductive toxicity, single dose toxicity was tested in male ICR mouse according to KFDA Guideline 1999-61 [KFDA, 1999] at a dosage level of 2,000, 1,000, 500, 250 and $125\;mg/kg/10m{\ell}$. In this study, mortalities, clinical signs, body weight changes and body weight gains, gross findings and weight of principal organs were detected during and/or after 14 days of single dosing. After 2 or 3 days of dosing, 1 or 2 animals in 2,000 and 1,000 mg/kg-dosing groups were died. Excitation and leaping response were observed as test article-treatment related clinical signs. These abnormal signs were restricted to 2,000 and 1,000 mg/kg-dosing groups and they were recovered to normal within 4 days after dosing in case of survivors. A significant decrease of body weight were observed in some periods of observation in 2,000 and 1,000 mg/kg-dosing group from 1 days after dosing compared to those of vehicle control group. A significant decrease of body weight gains were observed in observation periods in 2,000 and 1,000 mg/kg-dosing group compared to those of vehicle control group. Hypertrophy of heart and decoloration of kidney were observed as test article-treatment related gross findings. These abnormal findings were restricted to 2,000 and 1,000 mg/kg-dosing groups. A significant increase of absolute and relative heart and kidney weight were demonstrated in 2,000 mg/kg-dosing groups. LD50 in this study was detected as 2,242.42 mg/kg. ALD in this study was detected as 1,000 mg/kg and the target organ was considered as the heart and kidney.

• Toxicological Research
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• 제25권3호
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• pp.132-139
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• 2009

The toxicity test of ammonium persulfate was conducted to ensure of its potential toxic effects according to the single-dose acute oral toxicity study (OECD Guideline 423) and 90-day repeated dose sub-chronic oral toxicity study guideline (OECD Guideline 408) for establishing national chemical management system, and matching in the Globally Harmonized Classification System (GHS) category. In acute oral toxicity study, pasty stool, perineal contamination and temporary body weight decrease were observed after dosing 1st and 2nd challenge (300 mg/kg body weight). All test animals were dead within 6 hours after dosing at 3rd challenge (2000 mg/kg body weight). Therefore, the GHS class of test substance is considered class 4. In sub-chronic toxicity study, body weight changes, food consumptions, hematological, biochemical and pathological examination did not show any noticeable and significant differences between the administered (5, 20, 80 mg/kg body weight) and control (vehicle only) group animals. Based on these results, the no observed adverse effect level (NOAEL) is considered above 80 mg/kg body weight.

• Journal of Chest Surgery
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• 제38권11호
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• pp.761-772
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• 2005

배경: 인공심장판막 시술 후에 혈전색전증의 위험성을 감소시키기 위래서 치료범위의 INR을 유지하는 것이 중요하다. 이 연구의 목적은 약사에 의해서 운영되는 anticoagulation service (ACS)을 받는 한국 인공심장판막 외래환자에서 실제적인 용량 가이드라인을 제시하고자 하였다. 대상 및 방법: 1997년 3월에서 2000년 9월까지 서울대학교병원에서 ACS를 방문한 모든 환자의 의무기록을 후향적으로 검토하였다. 수술 후 6개월이 경과된 환자로 INR 2.0미만과 INR 3.0초과가 한 번 이상 있는 환자의 자료를 대상으로 하였으며 이전의 INR이 안정화되었고, 복약순응도가 확인되고, warfarin과 알려진 약물 또는 상호작용이 없는 경우로 목표 INR에 도달하기 위해서 용량 조절을 필요로 한 증례(총 688명, 1,782회 방문)를 분석하였다. Warfarin용량 조절 가이드라인을 제시하기 위해서 대동맥 판막치환술과 승모판 또는 이중판막 치환술을 받은 환자를 구별하여 각각 용량 조절 전의 INR, 평균 조절된 용량, 조절 후의 INR을 조사하였다. 결과: 이 연구에서는 1주일 총 투여량의 변화량(mg)에 근거한 warfarin 용량 조절(가이드라인 I)과 비율에 근거한 1주일 총 투여량 조절 가이드라인(가이드라인 II)을 제시하였고 가이드라인 I과 가이드라인 II의 유효성도 평가하였다. 모든 환자 군에서 가이드라인 I이 가이드라인 II보다 우수하였지만 가장 흔히 사용되는 중등도의 용량(1주 총 투여량$23\~47mg$)을 투여 받는 환자에서는 두 가이드라인 사이에 유의한 차이가 없었다 결론: 이 연구에서 제시된 가이드 라인은 심장판막수술을 받은 외래 환자에서의 warfarin 용량 조절에 유용할 것으로 생각된다.대한 치료 순응도가 높아졌다. 후 동율동 전환율이나 좌심방 수축능 회복에 좋은 결과를 보여주었다 그러나 향후 대상환자들에 대한 중장기적인 추적 관찰이 필요하리라 생각한다.pm1.6$일째에 관상동맥조영술을 시행하여 모든 도관의 개존율$(100\%=57/57)$을 확인하였다 수술 전 중재 술을 시행한 1개소에서는 중재술 부위의 재협착소견이 보여 수술 후 조영술시 재풍선확장술로 치료하였다. 수술 후 추적관찰(평균 $25\pm26$개월)동안 1예에서 심부전으로 사망하였다. 생존한 환자 24예에서 술 후 평균 $9.6\pm3$개월째에 관상동맥조영술을 시행하였고 이식도관이 string 징후를 보인 1예를 제외하고 모두 개존(56/57)되어 있었으며, 약물용출형 스탠트를 시행하기 이전의 12예의 중재술 중 2예에서 $50\%$ 이상의 스텐트 협착이 있었으나 흉통의 재발은 없었다. 결론: 하이브리드 관상동맥 우회 술은 수술위험도를 낮추기 위하여 최소절개 관상동맥우회술과 병합하여 시도될 수 있을 뿐 아니라, 선택적 환자들에서는 정중 흉골절개 관상동맥우회술과 병합하여 수술관련 유병률을 낮추고 심근의 완전 재관류화를 도모할 수 있었다.호도에서 가장 적절한 방법으로 사료된다.비위생 점수가 유의적으로 높은 점수를 나타내었다. 조리종사자의 위생지식 점수와 위생관리 수행수준의 상관관계를 조사한 결과, 위생지식의 기기설비위생은 위생관리 수행수준의 합계(p<0.01)에서 유의적인 상관관계(p<0.01)를 나타내었으며, 위생지식의 식중독 및 미생물은 위생관리 수행수준의 개인위생(p<0.01)과 유의적인 상관관계가 있는 것으로 나타났다 위생지식의 점수합계는 개인위생(p<0.05)과 식중독 및 미생물(p<0.

• 대한한의학회지
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• 제26권2호
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• pp.32-51
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• 2005

Objectives: To study the effect of Artemisiae Capillaris Herba extracts, that have been used as oriental medicine to treat liver disease, on the perinatal and lactational n;)productive toxicity of SD rats when administered by oral lavage. Methods: Female SD rats were dosed from 6 days of gestation to 3 weeks postpartum. This was conducted in accordance with the recommendations of the KFDA Guidelines for Detection of Toxicity to Reproduction for Medicinal Products. Results: No Artemisiae Capillaris Herba extracts treatment-related changes in clinical signs, mortalities, implantation number, dead fetus number, loss rate of fetus, number of live young, survival rate of fetus, sex ratio of live young, external anomalies, pregnancy periods, viability index, lactational index, survival rate of litters at 4 days after birth or delivery index were demonstrated in any dosed levels in this study. However, the body weight and gains, food consumption and absolute organ weights of brain, adrenal glands, liver, spleen, kidney, ovaries and heart were significantly increased in 2000 or 1000mg/kg-dosing groups and the relative organ Weights of adrenal glands were significantly increased in 2,000mg/kg-dosing groups. Therefore, it was concluded that this increase was natural according to growth. Also, no changes of gross findings, clinical signs, mortalities, body weight and gains, physical development results, necropsy findings, organ weight, faculty test, open filed test and water-filled simple T-maze test, copulation, fertility, pregnancy indices, body weight and gains during gestation periods, necropsy findings, corpora lutea number, implantation number, implantation rate, dead fetus number, post-implantation loss rate, live young, post-implantation survival rate, sex ratio of live young, external anomalies and individual body weights of live young were demonstrated in any dosed levels in this study. Conclusions: It is considered that the NOAEL (No-Observed-Adverse-Effect Level) for perinatal and lactational reproductive toxicity of Artemisiae Capillaris Herba extracts was up to 2000mg/kg/day because no changes of other perinatal and lactational reproductive indices were demonstrated.

• 셀메드
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• 제11권1호
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• pp.2.1-2.8
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• 2021

The clinical condition Amnesia causes difficulty in learning new information and the inability to recall past events. It is primarily concerned with recent memory loss. Majoon-e-Nisyan (MJN) is a polyherbal Unani formulation, present in a semi-solid form. It is widely used potent drug of the Unani System of Medicine (USM) for treating Nisyan (amnesia). In the present study polyherbal Unani formulation, MJN has been studied for its quality control and acute toxicity. Standardization (quality control) of drugs deals with drug identity, drug quality and purity determination. Standardization of MJN had been done as per the Unani pharmacopoeial parameters approved by World Health Organization (WHO) - Pharmacognostical parameters, Physico-chemical parameters, high-performance thin-layer chromatography (HPTLC), microbial load, aflatoxin, and heavy metals. Solvents and chemicals used in the study were of analytical grade and used instrument were calibrated. By conducting an acute oral toxicity study in rats, the safety of MJN was assessed. The limit test method of OECD guideline 425 was followed in the study. Results of standardization and standard operating procedures (SOPs) for preparation of MJN may serve as the standard reference in the future. The data generated in the study for the quality control of MJN proved the quality of formulation and shows that MJN is not toxic in rats following acute dosing up to 2000 mg/kg bw. The data obtained in the paper for MJN may be used as a standard guideline for preparation of the formulation which can save time, cost, and resources for future research endeavours.

• 대한수의학회지
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• 제44권3호
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• pp.367-371
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• 2004

This report describes the determination of ceftiofur residues in milk from treatment of lactating dairy cattle by intramuscular injection of three consecutive daily doses of about 1 mg /kg BW, the recommended label dosing. The separation of ceftiofur was achieved on $C_1_8$ reverse phase column. The mobile phase consisted of 0.1% trifluoracetic acid in water (A) and 0.05% acetic acid in acetonitrile (B) and grediently flowed at the flow rate of 0.4 mL/min. As a result of analysis of blank raw bovine milk samples, matrix interference was not shown. Limit of detection and limit of quantitaion was 0.5 ng/mL and 1 ng/mL, respectively. The values of precision and recovery satisfied the guideline of National Veterinary Research and Quarantine Service (NVRQS, Korea). The mean residual concentration of ceftiofur in milk did not exceed 3.71 ng/mL when ceftiofur was administered intramuscularly to lactating dairy cattle for 3 consecutive days at 1 mg/kg of BW per day. It is much lower than the proposed MRL (100 ng/mL) of ceftiofur in milk.

• 대한한의학방제학회지
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• 제16권1호
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• pp.65-78
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• 2008

Objectives : this study was to access the effect of Hyeonggaeyeongyotang water extracts, a polyherbal formula has been used as folk medicine, on the fertility and early embryonic development of male and female Wistar rats when administered by oral gavage. Methods : In male rats, Hyeonggaeyeongyotang extract were dosed 4 weeks before pairing and 2 weeks after mating including the mating periods up to termination after necropsy of the majority of the females. In female rats, they were dosed 2 weeks before pairing, and from Day 0 to Day 7 of gestation. This study was conducted in accordance with the recommendations of the KFDA Guideline [2005-60] for Detection of Toxicity to Reproduction for Medicinal Products. Results: 1. No Hyeonggaeyeongyotang extract treatment-related changes on the clinical signs and mortalities, the Food consumptions, the Body weights and gains were demonstrated in all dosed levels tested in this study except for 500ml/kg-dosing male group in which a significant(p<0.05) increase of body gains was detected during day 0-7 after dosing. 2. No Hyeonggaeyeongyotang extract treatment-related changes on the pre-coital intervals, the estrus cycles, the mating index, conception rate and fertility index were demonstrated in all dosed levels tested in this study. 3. No Hyeonggaeyeongyotang extract treatment-related gross findings on reproductive organs, the weights of reproductive organs, histopathological findings on reproductive organs, the corpora lutea number, implantation site number, live fetus number, number of resorpted embryo and pre-and post-implatation loss were demonstrated in all dosed levels tested in this study. Conclusions : Base on the results, it is considered that the NOAEL (No-Observed-Adverse-Effect Level) for fertility and early embryonic development toxicity of Hyeonggaeyeongyotang extract was under 2000ml/kg/day in Wistar male and female rats because there no treatment-related changes on the fertility and early embryonic developmental index were demonstrated in all dosed levels tested.