• Title/Summary/Keyword: Dosing

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Postmortem Blood and Tissue Concentration of Carisoprodol and Meprobamate (카리소프로돌 중독사의 치사혈중농도 및 조직분포)

  • Choi Hye Young;Choi Hwa Kyung;Lee Ju Seon;Woo Sang Hee;Lee Han Sun;Park Yoo Sin;Chung Hee Sun
    • Journal of The Korean Society of Clinical Toxicology
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    • v.1 no.1
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    • pp.34-39
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    • 2003
  • Carisoprodol (CSP) is commonly prescribed as a skeletal muscle relaxant. Recently, we encountered 7 suicidal cases in which carisoprodol was detected. We developed a rugged, sensitive, and specific method for the determination of CSP and meprobamate (MPB) by GC and GC/MS. Postmortem blood concentrations of CSP and MPB ranged 22.9-124.4 ,$\mu$g/ml and its metabolite, 26.8-144.5 ,$\mu$g/ml respectively. Among 7 cases studied, Only CSP was ingested in 4 cases and combination of CSP and dextromethorphan was ingested in 2 cases according to the case history and one case was with ethanol. The order of the tissue concentration of CSP and MPB was liver> kidney > brain, and the concentration of MPB was higher than that of CSP in all tissues. The MPB /CSP concentration ratios of urine, bile juice, liver, kidney, brain and blood were 15.7, 4.0, 1.2, 1.4, 1.4 and 1.0 respectively. There was a big difference in concentration of CSP and MPB in 7 cases due to differences in the amount of dose administered and time to death after dosing.

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Studies on Pharmacokinetics of a new NSAID SJ-151(I)

  • Kim, Dong-Sup;Chung, Hye-Joo;Na, Han-Kwang;Park, Yoon-Ju;In Sook, Park;Ahn, Mi-Lyung;Chang, Young-Sup
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.220-220
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    • 1996
  • The objectives of this study were to evaluate the pharmacokinetics of SJ-151 which is a new NSAID in male Beagle dogs following a single oral dosing. Seven beagle dogs (10-l2kg) were all administered a single oral gavage(10mg/kg) of SJ-151 tablet and serial blood samples of approximately 5$m\ell$ were then drawn from the cephalic vein of each animal at 0(predose), 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24hours postdosc. SJ-151 (Cinmetacinㆍbutendiol)and cimetacin were quantified in the plasma fraction by HPLC assay. The pharmacokinetic parameters calculated from the plasma concentrations of SJ-151 in dayl are Cmax(ng/$m\ell$)509$\pm$248, Tmax(hr) 1.50$\pm$0.45, AUC(ng.hr/$m\ell$) 1,750$\pm$762, tl/2$\alpha$ 0.98$\pm$0.30, t1/2$\beta$ 12.0$\pm$6.75. The pharmacokinetic parameters calculated from the plasma concentrations of Cinmetacin in day 1 are Cmax(ng/$m\ell$)258$\pm$74.1, Tmax(hr)2.42$\pm$ 0.92, AUC(ng.hr/$m\ell$) 1,820$\pm$318, t1/2$\alpha$ 1.74$\pm$0.49, t1/2$\beta$ 25.4$\pm$13.4.

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Targeted and sustained delivery of hydrocortisone to normal and stratum corneum-removed skin without enhanced skin absorption using a liposome gel

  • Kim, Moon-Kyoung;Chung, Suk-Jae;Lee, Min-Hwa;Cho, Ae-Ri;Shim, Chang-Koo
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.278-278
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    • 1996
  • Judging from hydrocortisone concentration in dosing area, the extent of absorption was reduced in the liposome-gel formulation. However, higher and sustained skin concentrations of hydrocortisone were achieved for the liposome-gel as compared to the ointment. Drug concentration in both viable and deep skin reached its maximum within 0.5 h after application of both formulations to both skin types. Drug concentrations in both skins from the ointment declined with time, while those from the liposome-gel were greatly sustained. The sustainment by the liposome-gel was more remarkable in the viable skin than in the deep skin. Drug concentration in the viable skin could be maintained at a nearly constant level for over 8 h by applying the liposome-gel. As a result, a 5-fold higher viable skin drug concentration was obtained from the liposome-gel than from the ointment at 8 h after the application to the SC-removed skin. However, the plasma concentration of hydrocortisone at 4 h from the liposome-gel was only one-fourth (p<0.01) the value from the ointment when the drug was applied to the SC-removed skin, consistent with. the lower urinary (one-third, p<0.05) and fecal (one-half, p<0.05) excretion. Conclusions : Retarded diffusion of the drug from the skin to the systemic blood stream appears to be a potential factor in the sustained skin concentration of hydrocortisone from the liposome-gel, Interaction of hydrocortisone in the skin with phosphatidylcholine, a component of the liposomes and skin, may well be a factor in retarding the diffusion of the drug in the skin.

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Micronucleus Test of Bupleuri Radix Aqueous Extract in Bone Marrow Cells of Male ICR Mice (시호 물 추출물의 마우스 골수세포를 이용한 유전독성 평가)

  • Cheon, Woo-Hyun;Chung, In-Kwon;Kang, Su-Jin;Ku, Sae-Kwang;Lee, Young-Joon
    • Korean Journal of Oriental Medicine
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    • v.18 no.2
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    • pp.151-157
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    • 2012
  • In this research, the genotoxic effect of Bupleuri Radix (BR), the dried roots of Bupleurum falcatum Linne has been traditionally used as anti-inflammatory agent, was evaluated using the mouse micronucleus test. BR aqueous extract (yield = 16.52%) was administered once a day for 2 continuous days by oral gavage to male ICR mice at doses of 2,000, 1,000 and 500 mg/kg. Cyclophosphamide (CPA) 70 mg/kg was used as a known genotoxic agent in a positive control. The appearance of a micronucleus (MN) in polychromatic erythrocyte (PCE) is used as an index for genotoxic potential, and PCE ratio is used as an index of cytotoxicity. Although significant (p<0.01) increase of the number of PCE with one or more nuclei (MNPCE) was detected in CPA treated groups, no significant increases of MNPCE numbers were observed in all three different dosages of BR extracts treated mice with over 0.30 of the individual polychromatic erythrocyte ratio in all mice used in this study. The results obtained indicated that BR extract shows no genotoxicity effects up to 2,000 mg/kg dosing levels the limit dosage in rodents.

Terato Genicity Test of Oral Administration of Artemisiae capillaris herba Extracts on New Zealand White Rabbit (인진(茵蔯)의 생식.발생 독성 시험 -배자(胚子)및 태자(胎子)발생을 중심으로-)

  • Roh, Heui-Mok;Kim, Seong-Mo
    • Korean Journal of Oriental Medicine
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    • v.16 no.2
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    • pp.143-157
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    • 2010
  • Objectives : The objective of this study was to access the effect of Artemisiae capillaris herba Extracts on the organogenetic reproductive toxicity of New Zealand White rabbits when administered by oral gavage. Methods : Gestational New Zealand White rabbits were dosed from 6 days of gestation to 18 days of gestation. It was conducted in accordance with the recommendations of the KFDA Guideline for Detection of Toxicity to Reproduction for Medicinal Products. In addition, serum AST, ALT, LDH and ALP levels were detected with their necropsy and histopathological observation Results: No significant changes of body weights, gains and food consumption were demonstrated in all dosed groups compared to those of vehicle control group except for 2,000mg/kg-dosing group, which showed significantly increase of body weight compared to that of vehicle control group. Normal gross findings were demonstrated in all tested groups. No significant changes of number of corpora lutea, implantation, implantation rate, number of fetal death, loss rate of post-implantation, number of live youngs at C-section, survival rate of post-implantation, number of male live youngs at C-section, number of female live youngs, sex ratio of live young, external anomalies of live youngs and body weight of live youngs were demonstrated in all dosed groups compared to those of vehicle control group. Although some visceral variations such as thymic reminant in the neck, dilation of renal pelvis, dilated ureter and malpositioned left common carotid artery, no significant changes were demonstrated in all dosed groups compared to that of vehicle control group. Some malformations and variation were demonstrated with retardations. However, no significant changes were demonstrated in all dosed groups compared to that of vehicle control group. In addition, similar ossification numbers were detected in sternebrae, metacarpals, metatarsals, phalanges, cervical vertebrae, and sacral and caudal vertebrae. No Artemisiae capillaris herba Extracts treatment-related changes of serum AST, ALT, LDH and ALP levels were demonstrated in all dosed levels in this study. Conclusions : We could conclude that oral administration of Artemisiae capillaris herba Extracts hasn't an influence on the organogenetic reproductive toxicity.

A Study on Optimization of Catalyst Injection Controller for Reducing Soot (Soot 저감을 위한 촉매 분사 최적화 방안 연구)

  • Kim Byeong-Woo
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.7 no.3
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    • pp.278-284
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    • 2006
  • The popularity of the diesel engine revolves around its fuel efficiency, reliability, and durability compared to the gasoline engine. However, the main disadvantage of diesel engine is the emission of particulate matter (PM) which is known as carcinogenic substance. Therefore recent progress in engine management and after-treatment systems has led to great improvement to satisfy strict emission regulations. To comply with powerful environment regulations, this study is focused on the decrease of PM(soot) as to increase significantly exhaust temperature. Therefore, HC injection is used as the method to go to the PM regeneration temperature in front of filters composed of diesel oxidation catalyst(DOC) and diesel particulate filter(DPF). And especially, LPG is used because it has good chemical reactions with exhaust. In this study, we could manufacture the test bench thought LPG injection - with which soot can be decreased-, construct 3 kinds of database(DB) according to quantity of temperature to decide the LPG injection quantity and develop DPF ECU algorithm.

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Effect of Banhasasim-tang on the Cardiac Toxicity and clinical symptom induced by Doxorubicin (반하사심탕(半夏瀉心湯)이 Doxorubicin에 의해 유발(誘發)된 심장독성(心臟毒性) 및 임상증상(臨床症狀)에 미치는 영향(影響))

  • Shin Min-Kyu;Hwang Hui-Jeung;Kim Sang-Chan;Byun Joon-Seok
    • Herbal Formula Science
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    • v.10 no.1
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    • pp.131-142
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    • 2002
  • The effect of Banhasasim-tang extracts on the cardiac toxicity and general symptom induced by Doxorubicin administration(Three injection protocol) were monitored using male ICR mice. The changes of body weight, clinical signs, necropsy findings and organ weights of heart were observed. The results were as followed. 1. Decrease of body weight after Doxorubicin treatment were dose-dependently inhibited by Banhasasim-tang extracts. 2. The degrees of anorexia, ataxia and dehydration that were observed in Doxorubicin treatment group were dose-dependently inhibited by Banhasasim-tang extracts. 3. Increase of absolute and relative heart weight observed in Doxorubicin treatment group were dose-dependently inhibited by Banhasasim-tang extracts. In addition. the degrees of heart congestion and enlargement were significantly and dose-dependently decreased after Banhasasim-tang extracts dosing groups compared to that of Doxorubicin treatment group. In conclusion, the toxicity of Doxorubicin treatment(decrease of body weights, clinical signs such as anorexia, ataxia and dehydration, changes of organ weights of heart) was inhibited and/or prevented by Banhasasim-tang extracts. According to these results. it is considered that Banhasasim-tang has some preventive effect against to toxicity induced by Doxorubicin.

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Single Dose Toxicity Test of Bojungikkeehapdaechilkitang water extract in Male and Female ICR Mice (보중익기합대칠기탕(補中益氣合大七氣湯) 추출물의 ICR마우스에서 경구 단회투여독성 평가)

  • Bae, Young-Chul;Choi, Bin-Hye;Kim, Dong-Woo;Hur, Jin-Il;Kim, Dae-Jun;Byun, Joon-Seok
    • The Journal of Internal Korean Medicine
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    • v.26 no.2
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    • pp.369-378
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    • 2005
  • An herbal water extract of Bojungikkeehapdaechilkitang(BDT) was prepared to test it for single-dose and repeated-dose toxicity, genotoxicity and reproductive toxicity, and to obtain a 50% lethal dose$(LD_{50})$, approximated lethal dose(ALD), and approximated target organs for BDT. The extract was tested on female and male ICR mice according to KFDA Guideline 1999-61 at doasge level of 2000, 1000, 500, 250 and 125mg/kg/10mL In this study, clinical signs, mortalities and gross findings of principal organs were observed for 14 days of single dosing, and afterwards in some cases. The ALD and $LD_{50}$ of BDT extract obtained in this study was>2000mg/kg for both male and female ICR mice. Also, any possible digestive toxicity of BDT extract was found to be above 1000mg/kg in both male and female ICR mice. The results of this study strongly suggest that BDT extract has no toxic effect at dosage level below 500mg/kg.

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Micronucleus Test of $Scutellariae$ $Radix$ Aqueous Extract in Bone Marrow Cells of Male ICR Mice (황금(黃芩) 물 추출물의 마우스 골수세포를 이용한 유전독성 평가)

  • Chung, In-Kwon;Cheon, Woo-Hyun;Kang, Su-Jin;Ku, Sae-Kwang;Lee, Young-Joon
    • Journal of Society of Preventive Korean Medicine
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    • v.16 no.1
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    • pp.81-89
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    • 2012
  • Objectives : In this research, the genotoxic effect of $Scutellariae$ $Radix$(SR), the dried roots of $Scutellaria$ $baicalensis$ Georgi has been traditionally used as antipyretic agent, was evaluated using the mouse micronucleus test. Methods : SR aqueous extract(yield = 27.2%) was administered once a day for 2 continuous days by oral gavage to male ICR mice at doses of 2,000, 1,000 and 500 mg/kg. Cyclophosphamide(CPA) 70 mg/kg was used as a known genotoxic agent in a positive control. The appearance of a micronucleus(MN) in polychromatic erythrocyte(PCE) is used as an index for genotoxic potential, and PCE ratio is used as an index of cytotoxicity. Results and Conclusions : Although significant(p<0.01) increase of the number of PCE with one or more nuclei(MNPCE) was detected in CPA treated groups, no significant increases of MNPCE numbers were observed in all three different dosages of SR extracts treated mice with over 0.33 of the individual polychromatic erythrocyte ratio in all mice used in this study. The results obtained indicated that SR extract shows no genotoxicity effects up to 2,000 mg/kg dosing levels - the limit dosage in rodents.

Single Oral Dose Toxicity Study of Water Extracts of Polygalae Radix in ICR Mice

  • Kang, Byung Hoon;Ku, Sae Kwang;Seo, Bu Il;Roh, Seong Soo;Park, Soo Jin;Park, Ji Ha
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.27 no.4
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    • pp.453-459
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    • 2013
  • The objective of this study was to evaluate the single oral dose toxicity of Polygalae Radix (PR) in male and female mice. PR extract (yield = 18.6%) was administered to ICR mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines (2009-116, 2009). Animals were monitored for the mortality and the changes in body weight, clinical signs and gross observation during 14 days after dosing. Upon necropsy, organ weight and histopathology of 14 principal organs were examined. It was observed that there were no mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principal organs related to PR extract up to 2,000 mg/kg. Therefore, 50% lethal dose ($LD_{50}$) and approximate LD of PR aqueous extracts after single oral treatment in female and male mice were considered over 2000 mg/kg the limited dosages recommended by KFDA Guidelines, respectively.