• Korean Journal of Clinical Pharmacy
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• v.6 no.2
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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.

• Herbal Formula Science
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• v.16 no.1
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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.

• The Journal of Internal Korean Medicine
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• v.27 no.1
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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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.2
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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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• v.25 no.3
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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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• v.38 no.11 s.256
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• pp.761-772
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• 2005

Background: Following the implantation of heart valve prostheses, it is important to maintain therapeutic INR to reduce the risk of thromboembolism. The objective of this study was to suggest a practical dosing guideline for Korean outpatients with prosthetic heart valves managed by a pharmacist-run anticoagulation service (ACS). Material and Method: A retrospective chart review was completed for all patients enrolled in the ACS at Seoul National University Hospital from March, 1997 to September, 2000. Patients who were at least 6 months post-valve replacement and had nontherapeutic INR value (less than 2.0 or greater than 3.0) were included. The data on 688 patients (1,782 visits) requiring dosing adjustment without any known drug or food interaction with warfarin were analyzed. The amount of adjusted dose and INR changes based on the INR at the time of the event were calculated. Aortic valve replacements (AVR) patients and mitral or double valve replacement (MVR/DVR) patients were evaluated separately. Result: Two methods for the warfarin dosage adjustment were suggested: Guideline I (mg-based total weekly dose (TWD) adjustment), Guideline II (percentage-based TWD adjustment). The effectiveness of Guideline 1 was superior to Guideline II overall in patients with both AVR and MVR/DVR. Conclusion: The guideline suggested in this study could be useful when the dosage adjustment of wafarin is necessary in outpatients with mechanical heart valves.

• The Journal of Korean Medicine
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• v.26 no.2 s.62
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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.

• CELLMED
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• v.11 no.1
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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.

• Korean Journal of Veterinary Research
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• v.44 no.3
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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.

• Herbal Formula Science
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• v.16 no.1
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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.