• Title/Summary/Keyword: oral doses

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Pharmacokinetics of DA-8159, a new PDE5 inhibitor, after single and 1-week repeated oral administrations in mice

  • Park, Kyung-Jin;Ahn, Gook-Jun;Kim, Dong-Hwan;Shim, Hyun-Joo;Ahn, Byung-Ok;Kim, Soon-Hoe;Kim, Won-Bae
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.245.1-245.1
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    • 2003
  • DA-8159 is a new PDEV (Phosphodiesterase V) inhibitor, synthesized by Dong-A Pharm., as an oral agent to treat male erectile dysfunction. To make a selection of the dosage of oral administration in carcinogenic studies, we studied preliminarily the pharmacokinetics of DA-8159 after single (at the 1$\^$st/ day) and 1-week (at the 7$\^$th/ day) oral administrations of the drug at doses of 15, 50 and 150 mg/kg/day, to male ICR mice. In 15mg/kg single and 1-week repeated oral administration groups, the concentrations of DA-8159 and DA-8164(the main metabolite of DA-8159) were below the limit of quantitation(LOQ:50ng/ml). (omitted)

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Acute Oral Toxicity of G. bimaculatus in Rats (랫드에 대한 G. bimaculatus의 급성경구독성시험)

  • 김인선;안미영;류강선;이병무
    • Toxicological Research
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    • v.18 no.4
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    • pp.397-400
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    • 2002
  • This study was carried out to investigate the acute toxicity of G. bimaculatus in Sprague-Dawley rats. G. bimaculatus was administered orally at doses of 8, 40, 200, 1000 and 5000 mg/kg. in this study, number of deaths, clinical sign, body weights, and pathological examination were investigated for 14 days after administration of G. bimaculatus. The results indicate that G. bimaculatus did not show any toxic effect in rats and oral $LD_{50}$ value was over 5000 mg/kg in Sprague-Dawley rats.

Pharmacokinetics of Haloperidol (III) -The Pharmacokinetics of Haloperidol after single oral and intravenous doses in schizophrenic patients- (Haloperidol의 약물속도론적 연구 (III) -정신분열증 환자에 있어서 Haloperidol의 일회 주사 및 경구투여시의 Pharmacokinetics-)

  • Park, Kyoung-Ho;Lee, Min-Hwa;Lee, Myung-Gull;Kwon, Jun-Soo;Park, Won-Myung;Park, Jin-Seng
    • YAKHAK HOEJI
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    • v.34 no.6
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    • pp.375-383
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    • 1990
  • The pharmacokinetics of haloperidol were determined after single oral and intravenous doses in 13 male schizophrenic patients. Plasma concentrations of haloperidol(HP) and reduced haloperidol(RH) were measured by high performance liquid chromatography. Plasma concentration data obtained were analyzed by obth model dependent (one-or two exponential decay models using nonlinear regression) and model independent (AUC and first moment curve) approaches. The two methods were found to be in close results. After intravenous injections of HP in 8 patients (10 mg/man), the mean central and peripheral volume of distributions were $2.85\;{\pm}\;1.70$ and $8.09\;{\pm}\;2.10\;l/kg$, respectively, and mean steady state volume of distribution was $11.87\;{\pm}\;3.21\;l/kg$. Mean clearance, MRT and elimination half life were $12.39\;{\pm}\;3.25\;ml/min/kg$, $925.10\;{\pm}\;166.79\;min$ and $676.35\;{\pm}\;126.45\;min$, respectively. After oral administrations of HP in 5 patients, mean peak time and peak concentration were $217.63\;{\pm}\;61.60\;min$ and $9.77\;{\pm}\;2.92\;ng/ml$, respectively. Mean MRT and elimination half life were $1112.23\;{\pm}\;131.73\;min$ and $724.02\;{\pm}\;120.03\;min$, respectively, and these parameters were not significantly different from those of intravenous injection of HP. Absolute bioavailability of HP oral product was found to be about 44%. The profiles of plasma RH concentration-time curves after oral or intravenous doses of HP were similar. Also it was found that the elimination rate of RH was solwer than that of HP by comparing the slopes of plasma concentration-time curves of HP and RH.

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Acute Oral Toxicity Studies of Extract of Sanghwang Mushroom (Phellinus linteus) (재배 상황버섯 추출물의 경구투여 급성독성 연구)

  • 한용석;박순영;최병기;정세영
    • Biomolecules & Therapeutics
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    • v.9 no.1
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    • pp.46-50
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    • 2001
  • The current study was performed to determine the acute oral toxicity of a crude extract of sanghwang mushroom (Phellinus linteus), in SD rats. 5 rats of each sex were orally treated with a single dose of extract of sanghwang mushroom at doses of 0, 500, 1,000, 2,000 mg/kg, respectively. After the treatment, clinical signs and body weight change, the food and water consumption were observed for 14 days. All animals survived during the study and did not show any clinical signs. Body weight gain showed no significant difference between the control and treated rats. However, body weight gain delayed in high dose group (2,000 mg/kg) on day 1~3 after administration. Another 5 rats of each sex were orally treated with a single dose of extract of sanghwang mushroom at dosages 4,000, 5,000 mg/kg respectively, but all animals survived during the study and did not show any clinical signs. It is suggested that LD$_{50}$ of extract of sanghwang mushroom by oral administration was estimated to be over 5,000 mg/kg in both sexes of rats.s.

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A 14-day Repeated Dose Oral Toxicity Study of HT042 in Sprague-Dawley Rats (Sprague-Dawley계 흰쥐를 이용한 HT042의 14일 반복 경구투여 독성연구)

  • Song, Jungbin;Lee, Donghun;Kim, Young-Sik;Lee, Seunggyeong;Bae, Jin-Sook;Kim, Hocheol
    • The Korea Journal of Herbology
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    • v.32 no.1
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    • pp.63-68
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    • 2017
  • Objectives : HT042 is a combination of three herbal extracts from the roots of Astragalus membranaceus, the stems of Eleutherococcus senticosus and the roots of Phlomis umbrosa, which has been demonstrated to increase longitudinal bone growth rate. The aim of this study was to assess the safety of HT042 after repeated oral administration. Methods : A 14-day repeated oral dose toxicity study was conducted using male and female Sprague-Dawley rats. HT042 was administered orally at repeated doses of 500, 1,000 and 2,000 mg/kg/day for 14 days. Clinical signs and mortality were observed daily, whereas body weight and food consumption were recorded weekly throughout the experiment. At the end of the study, blood was taken from the posterior vena cava for hematology and serum biochemistry. All organs of the body surface, subcutis, head, thoracic cavity, and abdominal cavity were observed grossly. Then, the internal organs were removed and weighed. Results : No death occurred and no significant changes in clinical sign, body weight, food consumption and serum biochemistry parameters were observed in male and female rats over the study period. Although there were some alterations in hematologic and necropsy findings, and organ weights, these changes were not considered toxicologically significant. Conclusions : These results suggest that the 14-day repeated administration of HT042 does not produce any significant oral toxicity at doses of up to 2,000 mg/kg/day in male and female rats under the present experimental conditions.

COMPARISON OF ABSORBED DOSES RESULTING FROM VARIOUS INTRAORAL PERIAPICAL RADIOGRAPHY (전악 치근단 방사선사진 촬영시 촬영조건에 따른 흡수선량 변화에 대한 연구)

  • Kang Mi-Ae;Park Tae-Won
    • Journal of Korean Academy of Oral and Maxillofacial Radiology
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    • v.25 no.2
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    • pp.297-308
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    • 1995
  • This study was designed to measure the absorbed dose to organs of special interest from full mouth with intraoral film(l4 films) and to compare the five periapical techniques. Thermoluminescent crystals(TLD-100 chip) were located in brain, orbit, bone marrow of mandibular ramus, bone marrow of mandibular body, bone marrow of 4th cervical spine, parotid gland, submandibular gland and thyroid gland. X -ray machine was operated at 70kVp and round collimating film holding device(XCP) and rectangular collimating film holding device(Precision Instrument) were used. The distance from the X-ray focus to the open end of the collimator was 8 inch, 12 inch and 16 inch. The results were as follows : 1. The absorbed dose was the highest in bone marrow of mandibular body(5.656mGy) and the lowest in brain (0.050mGy). 2. Generally, the lowest absorbed dose was measured from 16 inch cylinder, rectangular collimating film holding device with paralleling technique. But, in bone marrow of mandibular body and the floor of mouth, the highest absorbed dose was measured from 12 inch cylinder, rectangular collimating film holding device with paralleling techniques. 3. Comparing of five intraoral radiographic techniques, it was appeared statistically significant reduction of the absorbed doses measured with rectangular collimating film holding device compared to XCP film holding device (P<0.05). 4. No statistically significant reduction in the absorbed dose was found as cylinder length was changed(P>0.05).

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The enhancement of apoptosis by combined with proteasome inhibitor and DNA synthetic inhibitor in oral cancer

  • Lee, Young-Hee;Jung, Ji-Eun;Lee, Jung-Chang;Moon, Hyun-Ju;Lee, Nan-Hee;Jhee, Eun-Jung;Yi, Ho-Keun
    • International Journal of Oral Biology
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    • v.33 no.1
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    • pp.25-31
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    • 2008
  • Inhibition of proteasome activity may reduce many types of cancer, so it's pathway is effective in cancer as well as in clinical fields. Here the author has carried out experiment targeting on the elevation of apoptosis in oral cancer cells by combination of proteasome inhibitor, lactacystin, and DNA replication inhibitor, etoposide. The growth of KB cells was measured by MTT methods and apoptosis was analyzed by DNA fragmentation and Hochest nucleus staining. The proteasome activity was analyzed by fluorescent tagged peptide and cellular protein expression was detected by Western hybridization. Though lactacystin and etoposide inhibited KB cell growth alone, but low combined doses inhibited cell growth more strongly and induced apoptosis. The proteasome activity was also seriously inhibited by the combination of both chemicals. Tumor suppressor proteins and apoptosis inducing proteins were highly increased under the combination of both chemicals. From above studies we can conclude that proteasome inhibitors may be used for the treatment of oral cancer and proteasome inhibitors with DNA replication inhibitors may be effective in clinical trials of oral cancer.

RISK FACTORS FOR ORAL CANCER ; A CASE-CONTROL STUDY (구강암의 위험요인 분석을 위한 환자-대조군 연구)

  • Kwon, Ho-Keun;Cha, In-Ho;Lim, So-Jung;Choi, Choong-Ho;Kim, Baek-Il
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.28 no.5
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    • pp.395-400
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    • 2002
  • The purpose of this study was to investigate the relationship between oral cancer and such factors as smoking and drinking pattern, oral health status, dietary intake pattern, socio-economic status. Oral cancer patients and other disease patients who visited Yonsei University Dental Hospital from May to September in 2000 were selected as the study subjects. The numbers of cases and controls were 41, 108, respectively. Two groups were matched with age and sex for case control study. Oral examination and questionnaires survey was performed by the dentist. To assess the strength of associations between oral cancer and other variables, chisquare tests were performed. The results were as follows : 1. The durations of smoking and alcohol drinking were not related significantly with oral cancer. But the doses of smoking and alcohol intake increased the risk of oral cancer significantly(OR=2.52, 4.11, p<0.05). 2. Denture wearing, the number of missing teeth and spicy and salty food, coffee, tea and fresh fruit intake frequency did not significantly increase the risk of oral cancer. But low education level, residency in rural area increased risk of oral cancer significantly(p<0.01).

Thirteen-week repeated-dose oral toxicity study of the Modified Wenpitang-Hab-Wulingsan (WHW$^{(R)}$) in Sprague-Dawley rats (WHW$^{(R)}$의 랫드에서의 반복경구투여 독성에 관한 연구)

  • Oh, Tae-Woo;Sang, Bae-Hyo;Yoon, Cheol-Ho;Park, Yong-Ki
    • The Korea Journal of Herbology
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    • v.25 no.3
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    • pp.43-51
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    • 2010
  • Objectives : We investigated the repeated-dose toxicity of Wenpitang-Hab-Wulingsan(WHW), a Korean traditional medicine prescribed with twelve herbs, which has been used for the treatment of renal disease. Methods : WHW extract prepared by GLP company. WHW was supplemented by gavage at 0, 100, 500 and 1000 mg/kg/day for 13-week consecutive days. We recorded the clinical signs of toxicity, body weight, organ weights, hematology, gross and histological changes in target organs rats and clinical chemistry analysis for all rats. Results : WHW extract at all doses was shown no mortality or abnormal clinical signs in rats during at the observation period. Furthermore, there was no difference in body weight and food-take consumption, organ weight, gross pathological findings, and urine analysis among the groups of rats treated with different doses of WHW extract. The hematological analysis and clinical blood chemistry data were revealed no toxic effects from WHW-treated rats. Conclusions : The results suggest that WHW extract in rats is a wide margin of safety on a acute toxicity.

Gastroprotective Effect of Korean Rice-Wine (Yakju) (한국 전통약주의 위보호 효과)

  • Kim, Seung-Jin;Baek, Ji-Young;Park, Chan-Koo;Kim, Gye-Won
    • Korean Journal of Food Science and Technology
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    • v.36 no.5
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    • pp.818-822
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    • 2004
  • Gastroprotective effects of Korean rice-wine (Yakju) in two types of acute experimental gastric ulcer induced in rats and in mice were evaluated. Korean rice-wine were administered to 24-hr fasted rats 30 min before administration of 60% EtOH in 150 mM HCl or absolute ethanol. Korean rice-wine prevented formation of gastric ulcers induced by 60% EtOH in 150 mM HCl at oral doses of 250-1,000mg/kg and reduced gastric ulcers induced by absolute ethanol at oral doses of 62.5-1,000mg/kg, and inhibitory effect against 30% alcohol treatment for 7 days (twice/day). These results suggest Korean rice-wine have inhibitory effects on gastric lesion and ulceration.