• Clinical and Experimental Reproductive Medicine
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• 제29권4호
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• pp.259-267
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• 2002

Objective: This study was performed to compare the clinical outcomes of GnRH antagonist (Cetrorelix) single dose and multiple dose protocols for controlled ovarian hyperstimulation with GnRH agonist long protocol. Materials and Method: From September 2001 to March 2002, 48 patients (55 cycles) were performed controlled ovarian hyperstimulation for ART using by either GnRH antagonist and GnRH agonist. Single dose of 3 mg GnRH antagonist was administered in 15 patients (17 cycles, single dose group) at MCD #8 and multiple dose of 0.25 mg of GnRH antagonist was administered in 15 patients (18 cycles, multiple dose group) from MCD #7 to hCG injection day. GnRH agonist was administered in 18 patients (20 cycles, control group) by conventional GnRH agonist long protocol. We compared the implantation rate, number of embryos, and clinical pregnancy rate among three groups. Student-t test and Chi-square were used to determine statistical significance. Statistical significance was defined as p<0.05. Results: There were no significant differences in ampules of used gonadotropins, number of mature oocytes, obtained embryos between single and multiple dose group, but compared with control group, ampules of used gonadotropins, number of mature oocytes, obtained embryos were decreased significantly in both groups. Clinical pregnancy rate and implantation rate were not different in three groups. There were no premature LH surge and ovarian hyperstimulation syndrome in three groups. Multiple pregnancy were occurred 1 case in multiple dose group and 2 case in control group. Conclusions: GnRH antagonist is a safe, effective, and alternative method in the controlled ovarian hyperstimulation compared with GnRH agonist. Clinical outcomes and efficacy of both single and multiple dose protocol are similar between two groups.

• Toxicological Research
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• 제19권1호
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• pp.51-66
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• 2003

This study was performed to evaluate single and repeated-dose toxicities of Bee Venom Extracts (F1, F3) in Spraque-Dawley. F1 was injected subcutaneously to rat at dose levels of 0, 0.0002, 0.002, 0.02 mg/kg/day for single-dose toxicity study and repeated-dose toxicity study. F3 was injected subcutaneously to rat at dose level of 0, 0.003, 0.03, 0.3 mg/kg/day for single-dose toxicity study and repeated-dose toxicity study. In both studies, there were no dose related changes in mortality, clinical sign, body weight change, food and water consumption, opthalmoscopy, organ weights, urine analysis, biochemical examination, and hematological findings of all animals treated with Bee Venom (F1, F3). Gross and histopathological findings revealed no evidence of specific toxicity related to Bee Venom (F1, F3). These results suggest that the subcutaneous NOEL (No Observed Effect Level) of Bee Venom (F1, F3) may be over F1 -0.02 mg/kg, F3-0.3 mg/kg.

• 한국수정란이식학회지
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• 제12권2호
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• pp.195-202
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• 1997

The present study was carried out to evaluate the effect of superovulation treatments on ovarian responses, oocyte recovery rates and grades of collected oocytes using an ultrasound-guided transvaginal approach in Korean native cows. Superovulation in cows was induced with two different regimenes: 1) FSH-decreasing dose(n=8): the cows were received twice per day for three days of the total dose of 400 mg of FSH-p, 2) FSH-single dose(n=9): the cows were administrated a single dose of 400 mg of FSH-p in 25% PVP. The Observation of visible follicles and collection of oocytes were performed 12 hours following the last FSH in FSH-decreasing dose group and 48 hours after the FSH-single dose injection. All visible follicles larger than 6 mm were punctured and aspirated with a 6.5 MHz convex-array ultrasound transducer designed for intravaginal use. The mean number of visible follicles(> 6 mm) was significantly(P<0.05) higher in the FSH-decreasing dose treatment (22.811.9) and FSH-single dose treatment (20.612.0) groups than the non-treatment group(7.0$\pm$8). The mean recovery rate of oocytes was not significantly(P<0.05) different between the treatment and control groups, but the mean number of collected oocytes was significantly(P<0.05) higher in the FSH-decreasing dose treatment( 12.611.5) and FSH-single dose treatment (11.813.6) groups than the non-treatment group(3.7$\pm$0.5). In conclusion, the FSH-single dose treatment at superovulation in cows for ultrasound-guided aspiration might increase the number of aspiratable follicles and the recovery rate of follicular oocytes as the FSH-decreasing dose treatment.

• Biomolecules & Therapeutics
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• 제10권1호
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• pp.59-69
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• 2002

Recently, recombinant human erythropoietin (rHu-EPO) has been used to treat various types of anemia. YHB216 is a new rHu-EPO developed by Yuhan Research Institute. In this study, we investigated the single dose and 4-week repeated dose toxicity of YHB216 in Beagle dogs. In the single dose toxicity study, YHB216 was administered intravenously at single dose levels of 0 and 25,000 IU/kg to dogs (2 dogs/sex/group). There were no treament-related changes in survivals, clinical signs, body weight gain, hematological values, blood chemical values, and necropsy finding during experimental period. In the repeated dose toxicity study, YHB216 was administered intravenously to dogs for 4 weeks at the dose levels of 0, 100, 500, and 2,500IU／kg (3 dogs/sex／group). There were no toxicologically significant changes in clinical signs, body weights, food and water consumptions, ophthalmoscopy, urinalysis and blood chemistry. There were increased values of red blood cell, hemoglobin, and hematocrit at all treated groups. Spleen revealed increased weight and extramedullary hematopoiesis at 500 IU/kg or more. These changes are all considered to be Pharmacology-related effects and were recovered after 4-week recovery period. From these results, it is concluded that LD50 value was above 25,000 IU/kg in the single dose toxicity study of YHB216 in dogs and the no observed adverse effect level (NOAEL) was 100 IU/kg day in the repeated dose toxicity study of YHB216 in dogs.

• 대한한방내과학회지
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• 제34권4호
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• pp.349-361
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• 2013

Objectives : This study aimed to evaluate the single oral dose toxicity and four weeks repeated dose determination of Gamisasangja-tang (GST) in male and female Sprague-Dawley rats. Methods : In the single oral toxicity study, rats were orally administered a single dose of 0 and 5,000 mg/kg GST. There were 5 rats in each group. After single administration, mortality, clinical signs, body weight changes and gross pathological finding were observed for 14 days. In the 4-weeks repeated oral dose determination study, rats were orally administered a single dose of 0, 1,250, 2,500 or 5,000 mg/kg GST. There were 5 rats in each group. Mortality, clinical signs, body weight changes, food consumption and gross pathological finding were observed for 28 days. Organ weight, clinical chemistry and hematology were tested after 28 days. Results : There was no mortality in either of the two studies. There were also no significant differences in clinical sign, body weight, organ weights, hematological or serum chemical parameters between the GST and control groups. Conclusions : The results obtained in this study suggest that the 50% lethal dose of GST is over 5,000 mg/kg, so this finding would be expected to provide scientific evidence for the safety of GST.

• 동의신경정신과학회지
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• 제24권1호
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• pp.131-144
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• 2013

Objectives : To provide information on the safety of ACM, we carried out a single oral dose-increasing toxicity and 4-weeks repeated oral dose determining test of ACM in beagle dogs. Methods : In a single oral dose-increasing toxicity test, beagles were treated with ACM orally increasing dose level (1,000, 2,000, 5,000 mg/㎏) at interval of 3 days. After administration, signs of toxicity were observed for two weeks. In 4-weeks repeated oral dose determinating test, beagles were treated with ACM with oral dose 500, 1,000, 2,000 mg/kg for 4 weeks. Mortality, clinical signs, body weight changes, food consumption, urinalysis, hematological and biochemical parameters, organ weights, necropsy findings, and histological findings were monitored during the study period. Results : In a single oral dose-increasing toxicity test, we found no mortality, abnormalities in clinical signs, body weight, and necropsy findings during the study period. In 4-weeks repeated oral dose determinating test, we found no mortality, abnormalities in clinical signs, body weight, food consumption, urinalysis, hematological and biological parameters, gross findings, organ weights, necropsy findings, and histopathological findings in any of the beagles tested. Conclusions : The results obtained in these studies suggest that maximum tolerated dose (MTD) of ACM in male and female beagle dogs was supposed to be over 5,000 mg/kg. For the future studies of toxicity, it is advisable that high dose and low dose are set at 2000 mg/kg and 500 mg/kg, respectively.

• Journal of Gastric Cancer
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• 제14권3호
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• pp.156-163
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• 2014

Purpose: Information regarding antimicrobial prophylaxis (AMP) for gastric cancer surgery is limited. The present study investigated the efficacy of single-dose AMP for the prevention of surgical site infection (SSI) in patients undergoing gastrectomy for gastric carcinoma. Materials and Methods: Between 2011 and 2013, 1,330 gastric carcinoma surgery patients were divided into two AMP administration groups depending on the duration of treatment. Postoperative outcomes including morbidity and SSI were compared between the two groups overall and in matched patients. Risk factors for SSI were analyzed. Results: The extended group (n=1,129) received AMP until postoperative day 1 and the single-dose group (n=201) received single-dose AMP only during an operation. Postoperatively, there were no significant differences between the two groups with respect to overall morbidity, mortality, or length of hospital stay. The SSI rate of the single-dose group was not significantly different from that of the extended group overall (4.5% vs. 5.5%, respectively, P=0.556) or in matched patients (4.5% vs. 4.0%, respectively, P=0.801). There was no increase in the SSI rate of the single-dose group compared to the extended group in subgroups based on different clinicopathological and operative factors. Univariate and multivariate analyses revealed male gender, open surgery, and operating time (${\geq}180$ minutes) as independent risk factors for SSI. Conclusions: Single-dose AMP showed no increase in the postoperative SSI rate compared to postoperative extended use in patients undergoing gastrectomy for gastric carcinoma. The efficacy of single-dose AMP requires further investigation in randomized clinical trials specific to gastric cancer surgery.

• 혜화의학회지
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• 제22권1호
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• pp.171-184
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• 2013

Single-and repeated-dose toxicities of Compound K (CK) were evaluated according to Toxicity Test Guidelines of Korea Food and Drug Administration using Sprague-Dawley rats. For single-dose toxicity study, CK was dissolved in drinking water, orally administered and examined for 14 days. As results, CK up to a dose of 5,000 mg/kg, the limited dose, neither induced death, clinical signs and necropsy findings, nor affected body weight gain and organ weights, in which 10% lethal dose could not be estimated. Based on the results of single-dose toxicity test, CK was administered at doses of 500, 1,000 or 2,000 mg/kg for 28 days for the evaluation of repeated-dose toxicity. All doses including the limited dose (2,000 mg/kg) of CK did not cause any abnormalities of rats, including mortality, clinical signs, body weight gain, feed/water consumption, necropsy findings, organ weights, hematology, blood biochemistry. Rather, high doses (1,000 - 2,000 mg/kg) of CK reduced the serum levels of alanine transaminase (ALT), aspartate transaminase (AST), creatinine phosphokinase (CPK), lactate dehydrogenase (LDH) and triglycerides, in addition to an increase in glucose, indicative of protective effects on hepatic and muscular injuries. Thus, both maximum tolerable dose (MTD) and no observed adverse effect level (NOAEL) were not determined. The results indicate that long-term intake of high-dose CK might not induce general adverse effects.

• 동의생리병리학회지
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• 제28권2호
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• pp.186-194
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• 2014

The object of this study was to obtain acute toxicity information (single-dose oral toxicity) of Woohwangchungshim-won (WHCSW), a pill type herbal medicine used in Korean Medicine (KM) for treating stroke. In order to obtain the 50% lethal dose (LD50), approximate lethal dosage (ALD) and target organs, WHCSW powders were once orally administered to female and male ICR mice at dose levels of 2,000, 1,000, 500 and 0 (control) mg/kg (body weight.) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines (Notification No. 2009-116). The mortality and changes in the body weight, clinical signs and gross observation were monitored for 14 days after single-dose oral administration of WHCSW according to KFDA Guidelines with organ weights and histopathological changes were observed in 12 principle organs. After single-dose oral administration of WHCSW, we could not find any mortality and toxicological evidences up to 2,000 mg/kg-administered group, except for some accidental findings and dose-independent increases of body weight gains in female 1,000 and 500 mg/kg-administered female mice. The results obtained in this study suggest that the LD50 and ALD of WHCSW in both female and male mice after single-dose oral administration were considered as over 2,000 mg/kg because no mortalities were detected up to 2,000 mg/kg that was the highest dose recommended by KFDA and Organization for Economic Co-Operation and Development (OECD), and can be safely used in clinics.

• Journal of Pharmaceutical Investigation
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• 제39권2호
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• pp.111-115
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• 2009

The pharmacokinetics of cyclosporin A (CsA) after single and multiple oral dosing of new CsA self-micro-emulsifying drug delivery system (SMEDDS) in dogs were estimated. A single dose study was performed following a two-way crossover design against six dogs with reference SMEDDS. For a multiple dose study, three dogs were allocated for each drug, and 100 mg of drug was administered daily for 6 days. Whole blood concentration of CsA was analyzed by radio-immunoassay. Both drug showed identical blood concentration profiles in both studies, and no statistical difference was detected in pharmacokinetic parameters. The relative bioavailabilities of test SMEDDS were 91.4% and 89.1%, respectively, in the single dose study and the last day of multiple dose study. Especially, multiple dose study proved the good relationship between C-0/C-2 and AUC for reference SMEDDS, which is an indispensable part of therapeutic drug monitoring. These results suggest newly formulated CsA SMEDDS possibly shows identical pharmacokinetics and pharmacodynamic behaviors in clinical trials.