• 대한약학회:학술대회논문집
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• 대한약학회 2001년도 Proceedings of International Convention of the Pharmaceutical Society of Korea
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• pp.321.1-321.1
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• 2001

• Journal of Periodontal and Implant Science
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• 제25권3호
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• pp.470-477
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• 1995

Flavonoids from Scutellariae Radix possessed a dual function both as an anti-inflammatory agent and an enhancer of cellular activity in gingival fibroblast. The purpose of this study was to evaluate on the toxicity of ethanolic extract from the root of Scutellariae Radix Georgi and its flavonoids, Wogonin, Baicalein, and Baicalin were isolated and purified by the following method. The crude drug was extracted with ethyl acetate and the residue was dissolved in ethyl alcohol. The ethyl alcohol soluble fraction was separated, concentrated, and then chromatographed on a silica gel column. The acute oral LD 50 in rats was determined for EtOH ex. of Scutellariae Radix and three compounds were evaluated with a single oral gavage at three graded dosage levels. The acute intravenous LD 50 was determined with a single intravenous injection via the jugular vein at three graded dosage levels. Groups of 5 male and 5 female rats, 6 week of age at the start of the study, were fed diets containing 3 graded dosage levels for 14 days. Groups of 5 male and 5 female hamster received O.5ml of the test article at once in a day for 5 days to the buccal cheek pouch for two minutes each. The acute oral LD50 for EtOH ex. of Scutellariae Radix is 1430mg/kg, and for Wogonin 1320mg/kg, for Baicalein 1250mg/kg, for Baicalin 1330mg/kg. The acute intravenous toxicity of EtOH ex. of Scutellariae Radix and its extracts was found to be 27mg/kg body weight No toxic effects were observed in rats fed up to 200mg/kg of EtOH ex. of Scutellariae Radix, Wogonin, Baicalein and Baicalin in the diet for 14 days. The acute Mucouse Membrane LD 50 in hamsters was found to be greater than 100mg/kg. These results suggested that EtOH ex. of Scutellariae Radix and its flavonoids are safe for oral care products using limited amount of extract.

• 대한약침학회지
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• 제19권3호
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• pp.231-238
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• 2016

Objectives: This study used repeated intravenous injections of Saeng Maek San (SMS) injection in Sprague-Dawley (SD) rats to assess the toxicity and the stability of SMS. Methods: Six-week-old male and female SD rats reared by Orient bio Inc were chosen for this pilot study. They were randomly split into four groups: Group 1 (G1), the control group (0.3 mL of normal saline solution/day/animal), and Groups 2, 3 and 4 (G2, G3 and G4), the experimental groups (0.1, 0.2 and 0.3 mL/day/animal of SMS), respectively. Each animal received an intravenous injection of SMS once a day for four weeks. Clinical signs, body weight changes, and food consumption were monitored during the observation period, and urinalysis and hematology were conducted after four weeks of SMS or saline administration. Results: No deaths occurred in any of the four groups during the observation period. Compared to the control group, male and female rats in groups 3 and 4 (0.2 and 0.3 mL/animal/day) showed hemoglobinuria, but the low-dosage group (G2, 0.1 mL/animal/day) showed no significant changes in the clinical signs test. No significant changes due to SMS were observed in the experimental groups regarding body weight changes, food consumption urinalysis, or hematology. Conclusion: During this study, no mortalities were observed in any of the experimental groups and no hemoglobinuria was observed in the low dosage group (0.1 mL/animal/day) while it was intermittently observed in groups 3 and 4 (0.2 and 0.3 mL/animal/day). Thus, we suggest that the no-observed adverse-effect level (NOAEL) is 0.1 mL/animal/day in male and female SD rats.

• Journal of Pharmaceutical Investigation
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• 제36권6호
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• pp.363-369
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• 2006

Granisetron is a selective 5-HT3 receptor antagonist that is used therapeutically for the prevention of vomiting and nausea associated with emetogenic cancer chemotherapy. Although this drug is commercially available for intravenous and oral dosage, there is a need for intranasal delivery formulations in specific patient populations in which the use of these dosage forms may be unfeasible and/or inconvenient. A rapid and specific high-performance liquid chromatography method with mass spectrometric detection(LC-MS) was developed and validated for the analysis of granisetron in plasma after nasal administration in rats. This method has been validated for concentrations ranging from 5 to 1000 ng/ml with simple treatment. This technique has high level reproducibility, accuracy, and sensitivity. The method described was found to be suitable for the analysis of all samples collected during preclinical pharmacokinetic investigations of granisetron in rats after nasal administration. This study was aimed to investigate the feasibility of nasal delivery of granisetron for the elimination of vomiting. The effects of osmolarity, dosage volume at the same dose and applied dose on the nasal absorption of granisetron in rats were observed. No significant difference in the effect of osmolarity and dosage volume at the same dose was observed. As the applied dose of granisetron in nasal formulation increased, the absorption increased linearly. Based on these results it appears that only the applied dose(drug mass) determines the nasal absorption of granisetron. The bioavailability of granisetron on nasal administration of 4 mg/kg appeared to be comparable to that of intravenous administration of the same dose. These results suggest that granisetron can be efficiently delivered nasally and the development of nasal formulation will be feasible.

• 대한소아치과학회지
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• 제32권3호
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• pp.416-426
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• 2005

소아환자는 치과치료시 다양한 방법의 진정요법이 요구된다. 정맥내 투여방법은 약효의 발현이 빠르고, 진정의 심도 및 시간을 술자의 의도대로 조절할 수 있다는 장점이 있다. Midazolam은 현재 의과 및 치과영역에서 성인의 진정요법에 가장 널리 쓰이며, 심혈관계와 호흡계에 대한 영향이 적은 진정 약제이다. 그러나 midazolam을 이용한 정맥내 진정요법의 소아치과에서의 사용에 대한 연구와 보고는 적은 편으로, 이에 본 연구에서는 소아환자에서의 midazolam을 이용한 정맥내 투여시 효과적이고 안전한 초기 투여용량에 관한 연구를 하고자 한다. 진정요법으로 2회 이상의 구치부 치료가 필요한 건강하고 비협조적인 행동을 보이는 16명의 환자를 대상으로 하였으며 평균연령은 $54.7{\pm}10.7$개월, 평균 몸무게는 $18.1{\pm}3.0kg$이었다. 술전 투약으로 0.3mg/kg, 최대 5mg의 midazolam을 근육내 투여 후 30~50%의 $N_2O-O_2$를 병용투여한다. 이중 맹검법에 의해 모든 환자는 두 번의 내원 중 임의로 한번은 0.1mg/kg(I군)을, 다른 한번은 0.2mg/kg(II군)의 초기 용량의 midazolam을 정맥내 투여하여 치료하였고, 추가투여시에는 초기용량의 1/2을 투여하였다. 치료시 환자의 생징후를 측정하였고, 행동양상은 Ohio State University Behavioral Rating Scale과 Automated Counting System을 사용하여 평가하였다. 술자는 Houpt가 제시한 기준을 응용하여 임상적 치료의 성공과 실패를 평가하였다. 몸무게에 대한 총 투여용량은 I군에서 0.16mg/kg, 2군에서 0.24 mg/kg 이었다. 생징후의 경우 두 군 모두 정상범위 내에서 안정된 상태를 보였고, 통계적으로 유의한 차이를 보이지 않았다(p>0.05). 행동양상평가에서 II군에서 바람직한 행동양상(Quiet)의 비율이 높았고, 임상적 성공률은 II군에서 높았으나, 두 군간 통계학적 유의차는 보이지 않았다(p>0.05). 작용 발현시간은 II군에서, 회복시간은 I군에서 빨랐고, 약물 투여 횟수는 I군에서 많았으나, 두 군간 통계학적으로 유의한 차이를 보이지 않았다(p>0.05).

• The Korean Journal of Physiology and Pharmacology
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• 제16권4호
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• pp.273-279
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• 2012

Busulfan is an antineoplastic agent with a narrow therapeutic window. A post-hoc population pharmacokinetic analysis of a prospective randomized trial for comparison of four-times daily versus once-daily intravenous busulfan was carried out to search for predictive factors of intravenous busulfan (iBu) pharmacokinetics (PK). In this study the population PK of iBu was characterized to provide suitable dosing recommendations. Patients were randomized to receive iBu, either as 0.8 mg/kg every 6 h or 3.2 mg/kg daily over 4 days prior to hematopoietic stem cell transplantation. In total, 295 busulfan concentrations were analyzed with NONMEM. Actual body weight and sex were significant covariates affecting the PK of iBu. Sixty patients were included in the study (all Korean; 23 women, 37 men; mean [SD] age, 36.5 [10.9] years; weight, 66.5 [11.3] kg). Population estimates for a typical patient weighing 65 kg were: clearance (CL) 7.6 l/h and volume of distribution (Vd) 32.2 l for men and 29.1 L for women. Inter-individual random variabilities of CL and $V_d$ were 16% and 9%. Based on a CL estimate from the final PK model, a simple dosage scheme to achieve the target $AUC_{0-inf}$ (defined as median AUC0-inf with a once-daily dosage) of 26.18 $mg/l{\cdot}hr$, was proposed: $24.79{\cdot}ABW^{0.5}mg$ q24h, where ABW represents the actual body weight in kilograms. The dosing scheme reduced the unexplained interindividual variabilities of CL and Vd of iBu with ABW being a significant covariate affecting clearance of iBU. We propose a new simple dosing scheme for iBu based only on ABW.

• Toxicological Research
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• 제14권3호
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• pp.443-452
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• 1998

This sutdy was carried out to investigate the acute toxicity and foru-week intravenous toxicity of the intralipidos in rats and rabbits. The acute toxicity study of Intralipidos was performed in Spragur-Dawley (SD) rats. Intralipidos was administered by intravenous to maximum dose 200 ml/kg. $LD_{50}$ of intralipidos was found 139.5ml/kg and 153.8ml/kg in male female SD rats. Four-week toxicity of intralipidos using New Zealand White Rabbit and SD rats. The Rabbit and Rats were administered by intravenous seven days per week for 28 days, with dosage of 15, 6, 2 ml/kg/day and 20, 6, 2ml/kg/day, respectively. Animals treated with intralipidos did not cause any death and show any clinical signs. They did not show any significant changes of body weight, feed uptake and water consumption. They were not significantly different from the control group in urinalysis, ocular examination hematological, serum biochemical value and histopathological examination. Therefore, Intralipidos was not indicated to have any toxic effect in the Rabbits and Rats, when it was administrated by intravenous below the dosage 15ml/kg/day and 20 ml/kg/day for four weeks.

• 한국임상수의학회지
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• 제8권1호
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• pp.81-91
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• 1991

This study was carried out to investigate the effects of intravenous drip with ketamine hydrochloride and its application for control depth and maintenance of anesthesia in dogs. Changes of blood pressure, vital signs, blood gas and anesthetic state were observed in this study. The obtained were summerized as follows ; 1. Changes of blood pressure and heart rate after intravenous drip anesthesia with ketamine hydrochloride were observed with significant increase in all group ; group II (0.135m81k9/min), group III (0.269mg/kg/min) and group IV(0.538mg/kg/min). These conditions were maintained unchangeably until 160 minutes after administration in all group. This may be indicated that there were no side effects on account of ketamine accumulation. 2. There were irregular respiration, pain reflex, Jaw tone reflex and vomition probability in the anesthetic conditions of group II The anesthetic conditions of group III were rarely shown as mentioned above. Awakening time and recovery time of group H were more prolonged 21 minutes and 27 minutes respectively than those of group III. These experimental data suggested that the optimal dosage of intravenous drip anesthesia of ketamine Hcl was 0.269mg/kg/min.

• Toxicological Research
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• 제13권4호
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• pp.423-433
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• 1997

The acute and subacute toxicity of water soluble dimethyl dimethoxy biphenylate derivative (new DDB), hepatitis therapeutics, were investigated in SD rats. In the acute toxicity study, body weights and clinical signs were observed for 7 days after the intravenous injection of new DDB at doses of 140, 182, 236, 307 and 400 mg/kg(r=1.3). Death. Severe convulsion, tremor and decrease motor activity were observed in almost treated groups (except the 140 mg/kg treated group). Changes of body weight in treated groups were not significantly different from control group. Autopsy of survived animals revealed no abnormal gross findings related to new DDB. As a results, the $LD_{50}$ values of new DDB were 244.1 mg/kg for male and 232.5 mg/kg for female. In subacute toxicity study, body weights and clinical signs were observed after intravenous injection of new DDB at doses of 57, 75 and 100 mg/kg/day for 28 days. Death, decrease motor activity and tremor were observed above 75 mg/kg treated groups. Statistically significant changes were observed in hematological and biochemical parameters of new DDB-treated groups; however, these changes were within normal range and had no relationship with dosage. Several abnormal findings were observed in microscopic examination of tissue; however, these findings were not caused by new DDB but environmental factor. The no toxic dose level of new DDB were estimated to be 57 mg/kg/day in this study.

• Toxicological Research
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• 제12권1호
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• pp.113-119
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• 1996

Group of 40 male and 40 female Sprague-Dawley rats was given daily intravenous injections of different dosage of Ginkgo biloba extract(EGb 761), 7.5 mg/kg/day (low dosage group), 15 mg/kg/day (middle dosage group), or 30 mg/kg/day (high dosage group)for 3 month by tail vein according to Established Regulation of Korean National Institute of Safety Research (1994. 4. 14). Appearance, behavior, mortality, and food consumption of rats of treated groups were not affected during the experimental periods. No significant Ginkgo biloba extract(EGb 761)-related changes were found in urinalysis, hematology, serum chemistry, and organ weight. No histopathological lesions were seen in both control and treatment groups. Our results strongly suggest that no toxic changes were found in rat treated intravenously with Ginkgo biloba extract(EGb 761)for 3 month.