• Toxicological Research
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• 제8권1호
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• pp.41-48
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• 1992

The actue toxicity of a recombinant granulocyte macrophage colony-stimulating factor (code name: LBD-005) was evaluated in both sexes of Sprague-Dawley rats, 4 weeks old, by the oral, subcutaneous and intravenous routes of administration. LBD-005 in the acute toxicity study in the rats was not considerde to induce any toxicological effect on the rats in mortalities, clinical findings, body weights and gross findings. It is suggested that $LD_{50}$ values in rats would be >48 mg/kg in the oral route and >12 mg/kg in the subcutaneous or intravenous route.

• 약학회지
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• 제40권2호
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• pp.202-211
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• 1996

Experiments were performed on male Sprague-Dawley rats to investigate the immunobiological effects on route of administration of amygdalin(AM). Rats were administered orally at 12.5, 25, or 50mg/kg/day of AM or injected wtih 25,50, or 100mg/kg/day of AM intravenously for 2 weeks. Rats were immunized and challenged with sheep red blood cells(SRBC). The results of this study were summarized as follows;(1) In oral administration of AM, body weight gains were significantly increased by 50mg/kg AM as compared with controls, the relative weights of liver and thymus also were significantly increased by 12.5 and 25mg/kg AM. However, 2-mercaptoethanol-resistant hemagglutination titier (2-MER HA), Plaque forming cells (PFC) and rosette forming cells (RFC) were non-dose dependently decreased. Phagocytic activity and delayed-type hypersensitivity (DTH) reaction also were significantly decreased by 50mg/kg AM. (2) In intravenous injection of AM, body weight gains, hemagglutination titer (HA), 2MER-HA, DTH reaction, PFC, RFC and circulating leukocytes were not influenced by AM. However, the relative weights of liver, spleen and thymus were significantly enhanced 100mg/kg AM. These results indicated that oral administration of AM non-dose dependently suppresses humoral and cell-mediated immunity in SD rats, and that intravenous injection of AM is unaffected humoral and cell-mediated immunity, however, the high dose of it significantly enhances phagocytic activity.

• 생약학회지
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• 제40권1호
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• pp.35-40
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• 2009

The immunomodulatory activities of the ethanol extract of Gynostemma pentaphyllum, termed hereafter as GPE, were examined in immunosuppressed mice as well as in normal mice in the present study. Oral administration of GPE into mice prevented dexamethasone (DEX)-induced immunosuppression as determined by the mitogen-induced proliferation of the splenocytes and the the cytokine production (TNF-$\alpha$, IL-$1{\beta}$) in the whole blood culture. In addition, oral administration of GPE increased antitumor host defense in mice implanted with sarcoma-180 tumor cells. The immunoaugmenting activity of orally administered GPE was also confirmed in mice immunized with ovalbumin (OVA). Mice that were orally administered with GPE generated much more potent OVA-specific cytotoxic T lymphocyte (CTL) responses upon intravenous OVA injection compared to the untreated controls. These results demonstrate that oral administration of the ethanol extract of Gynostemma pentaphyllum could be useful to increase host defense in immunocompromised situations such as stress- or tumor-induced immunosuppression.

• 대한임상독성학회지
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• 제10권2호
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• pp.97-102
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• 2012

Purpose: Serious acetaminophen (AAP) poisoning causes hepatotoxicity. N-acetylcysteine (NAC) is the most effective therapy for AAP poisoning and can be administered orally and intravenously (IV). Several studies have compared the efficacy of these two routes of administration and the results have been controversial. The purpose of this study was to compare the efficacy of oral and IV NAC for the prevention of hepatic toxicity in Korean patients whose serum AAP levels were higher than normal. Methods: A retrospective before/after study was performed, in which the patients presented to the emergency department with an AAP overdose from February 1995 to March 2012. A 3-day oral NAC regimen was used in the beginning, and a 20-hr intravenous regimen was then used from 2007. This study assessed the complications of an AAP overdose, such as hepatotoxicity, hepatic failure and renal failure as well as the side effects of the treatment regimen. Results: A total of 41patients was enrolled in this study. The median ALT and AST were 63 (IU/L) and 57 (IU/L) for the oral NAC treated patients, and 14 (IU/L) and 20 (IU/L) for the IV NAC treated patients (p=0.004 and p=0.001, respectively). The incidence of complications was similar in the treatment groups (p=0.399). Among the patients, 7 patients developed hepatotoxicity and were treated successfully with oral or IV NAC. Conclusion: This study suggests that IV NAC and oral NAC can prevent and successfully treat hepatic toxicity in patients whose serum AAP levels are higher than normal.

• Archives of Pharmacal Research
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• 제26권1호
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• pp.89-94
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• 2003

In vivo clearance of BMS-182874 was primarily due to metabolism via stepwise N-demethylation. Despite in vivo clearance approached ca 50％ of the total liver plasma flow, BMS-182874 was completely bioavailable after oral administration in rats. Saturable first-pass metabolism and the role of extrahepatic tissue were evaluated as possible reasons for complete oral bioavailability despite extensive metabolic clearance. Pharmacokinetic parameters were obtained after an intravenous and a range of oral doses of BMS-182874 in rats. Bile and urine were collected from bile-duct cannulated (BDC) rats and the in vivo metabolic pathways of BMS-182874 were evaluated. Pharmacokinetics of BMS-182874 were also compared in nephrectomized (renally impaired) vs. sham-operated control rats. Oral bioavailability of BMS-182874 averaged 100％, indicating that BMS-182874 was completely absorbed and the first-pass metabolism (liver or intestine) was negligible. The AUC and C/sub max/ values increased dose-proportionally, indicating kinetics were linear within the oral dose range of 13 to 290 mmole/kg. After intravenous administration of BMS-182874 to BDC rats, about 2％ of intact BMS-182874 was recovered in excreta, indicating that BMS-182874 was cleared primarily via metabolism in vivo. The major metabolite circulating in plasma was the mono-N-desmethyl metabolite and the major metabolite recovered in excreta was the di-N-desmethyl metabolite. In vivo clearance of BMS-182874 was significantly reduced in nephrectomized rats. These observations suggest saturable first-pass metabolism is unlikely to be a mechanism for complete oral bioavailability of BMS-182874. Reduced clearance observed in the nephrectomized rats suggests that extrahepatic tissues (e.g., kidneys) may play an important role in the in vivo clearance of xenobiotics that are metabolized via N-demethylation.

• Biomolecules & Therapeutics
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• 제25권5호
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• pp.553-558
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• 2017

Paclitaxel (PTX) is one of the most frequently used anticancer agent for treating refractory ovarian cancer, metastatic breast cancer and non-small cell lung cancer. However, its oral administration is impeded by very low bioavailability (<5%) due to the P-glycopprotein (P-gp) efflux pump effect. This study investigated in vitro and in vivo P-gp inhibitory effects of adamantyl derivatives AC-603 and AC-786 in rats. Two adamantyl derivatives tested in this study increased the cytotoxicity of daunomycin (DNM) in P-gp overexpressed cell line by inhibiting P-gp efflux function. Pharmacokinetics of PTX with orally co-administered P-gp inhibitors were assessed in rats to improve PTX absorption. The pharmacokinetic parameters of PTX were determined in rats after intravenous (2 mg/kg) or oral (25 mg/kg) administration in the presence or absence of verapamil (a positive control), AC-603 or AC-786 (0.5 mg/kg or 5 mg/kg). Compared to control group (PTX alone), experimental groups (PTX with AC-603 or AC-786) significantly increased the area under the plasma concentration-time curve of PTX following oral administration by 1.7-2.2 fold. The volume of distribution and total clearance of PTX were decreased, while other parameters were not significantly changed. In conclusion, co-administration of AC-603 or AC-786 enhanced the relative bioavailability of orally administered PTX as compared to control.

• 농약과학회지
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• 제17권3호
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• pp.193-199
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• 2013

Burkholderia pyrrocinia CAB08106-4은 Sclereotium cepivorum와 Sclereotium sp.균주에 의해 발생하는 마늘 흑색썩음균핵병에 대한 항박테리아 효능을 가지고 있다. 이는 Sclereotium cepivorum와 Sclereotium sp.에 의해 발생하는 마늘 흑색썩음균핵병을 포함한 다양한 식물병원체를 관리하고 예방하는데 있어 친환경적인 미생물 제품이다. 이번 시험의 목적은 Burkholderia pyrrocinia CAB08106-4를 경구, 호흡기, 정맥에 대한 단회투여 시의 급성독성 증상과 병원성을 비교하고 평가하고자 한다. 급성독성/병원성 시험에서 랫드를 3, 7, 14, 21일에 안락사하여 체내 미생물잔존상황을 관찰하였고, 투여 후 21일 동안 매일 임상증상 관찰과 체중증가량을 평가하였다. 이번 시험에서 전체 시험기간 동안 투여군에 있어서 사망례는 물론 시험물질 투여와 관련된 임상증상은 관찰되지 않았고 체중도 정상적으로 증가한 것으로 관찰되었다. 미생물의 체 내외 관찰결과에 있어서도 모든 군에서 미생물은 검출되지 않았으며, 생존동물을 부검 관찰한 병리소견에서도 Burkholderia pyrrocinia CAB08106-4 투여와 관련된 이상은 관찰되지 않았다. 이상의 결과를 통해 급성경구, 급성호흡기 및 급성정맥 시험에서 투여된 미생물의 시험물질은 독성과 병원성에 문제가 없는 것으로 평가되었다.

• Pediatric Infection and Vaccine
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• 제5권1호
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• pp.147-151
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• 1998

On the treatment of Kawasaki disease, approximately 10% of children treated with IVIG have persistent or recrudescent fever despite IVIG treatment. We had experienced two children with Kawasaki disease who did not respond after multiple dosages of IVIG. They were treated within the first 10 days of onset of fever and were given oral aspirin (100mg/kg/day) and IVIG(2gm/kg) in a single infusion for 8 to 10 hours. The first child had not resolution of symptoms after three intravenous doses of IVIG(total 4gm/kg). And then treated with high dose methylprednisolone(30mg/kg) for 2 to 3 hours intravenously without symptoms improvement. On fifth hospital days, he was retreated with IVIG (2gm/kg) again with ultimate resolution of symptoms. The second child had resolution of symptoms after three intravenous doses of IVIG(total 4gm/kg). No adverse events were associated with the administration of IVIG or steroid. We reported two cases of IVIG non-responded Kawasaki disease with a brief review of the related literatures.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제36권5호
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• pp.408-412
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• 2010

Introduction: This study examined the depth of sedation and the usefulness of the monitoring tool in determining the level of sedation in patients undergoing third molars extraction under conscious sedation with midazolam. Materials and Methods: Twenty two patients undergoing third molars extraction at the department of Oral and Maxillofacial surgery, Ewha Womans Mokdong Hospital from February 2010 to April 2010 were analyzed. All patients were classified as American Society of Anesthesiologist (ASA) class I and had no contraindications tosedation. The bispectral index was recorded continually during surgery using a bispectral monitor. The initial sedation was accomplished using a 3 mg bolus of midazolam followed by a 2 mg bolus of midazolam until the level of sedation, at which the patient’s eyes were closed or the subject was responsive only to loud or repeated calling of their name, was reached. All subjects were surveyed with a postoperative questionnaire to evaluate the level of sedation. Results: The bispectral index (BIS) decreased approximately 5 minutes after midazolam administration, but increased at the local anesthesia injection and odontomy procedure. The amnestic effect was shown effectively in the early stages of surgery. Conclusion: Conscious sedation with intravenous midazolam is effective in achieving the effect of anxiolysis, analgesia and amnesia. The BIS is an objective and useful means of assessing the depth of sedation.

• Journal of Pharmaceutical Investigation
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• 제41권5호
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• pp.273-278
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• 2011

The aim of this study was to investigate the effect of efonidipine on the pharmacokinetics of warfarin after oral and intravenous administration of warfarin in rats. Warfarin was administered orally (0.2 mg/kg) or intravenously (0.05 mg/kg) without or with oral administration of efonidipine (1 or 3 mg/kg) in rats. The effect of efonidipine on the cytochrome P450 (CYP) 3A4 activity was also evaluated. Efonidipine inhibited CYP3A4 enzyme activity with 50% inhibition concentration ($IC_{50}$) of $0.08{\mu}M$. Compared to those in the oral control group (warfarin without efonidipine), the area under the plasma concentration-time curve (AUC) of warfarin was significantly greater (1 mg/kg, P<0.05; 3 mg/kg, P<0.01) by 25.9-59.0%, and the peak plasma concentration ($C_{max}$) was significantly higher (3 mg/kg, P<0.05) by 26.2% after oral administration of warfarin with efonidipine, respectively. The total body clearance of warfarin was significantly (3 mg/kg, P<0.05) decreased by efonidifine. Consequently, the relative bioavailability of warfarin was increased by 1.26- to 1.59-fold and the absolute bioavailability of warfarin with efonidipine was significantly greater by 59.7-75.4 % compared to that in the control group (47.4%). In contrast, efonidipine had no effect on any pharmacokinetic parameters of warfarin given intravenously. Therefore, the enhanced oral bioavailability of warfarin may be due to inhibition of CYP 3A4-mediated metabolism in the intestine and/or liver and to reduction of total body celarance rather than renal elimination, resulting in reducing first-pass metabolism by efonidipine.