• Journal of Pharmaceutical Investigation
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• 제31권4호
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• pp.281-287
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• 2001

Rebamipide is a novel anti-gastric ulcer agent that has been reported to increase the synthesis of mucus, to increase the mucosal concentration of prostaglandin, and to promote rapid ulcer healing. The purpose of the present study was to evaluate the bioequivalence of two rebamipide tablets, $Mucosta^{TM}$ (Otsuka Korea Pharmaceutical Co., Ltd.) and $Rebamide^{TM}$ (Kyung Dong Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The rebamipide release from the two rebamipide tablets in vitro was tested using KP VII Apparatus II method at pH 6.8 dissolution media. Twenty normal male volunteers, $24.20{\pm}2.26$ years in age and $66.19{\pm}9.41\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 100 mg of rebamipide was orally administered, blood was taken at predetermined time intervals and the concentrations of rebamipide in serum were determined using HPLC method with fluorescence detector. The dissolution profiles of two rebamipide tablets were very similar at pH 6.8 dissolution media. Besides, the pharmacokinetic parameters such as $AUC_t$, $C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t$, $C_{max}\;and\;T_{max}$ between two tablets based on the $Mucosta^{TM}$ were -2.57%, 5.77% and -1.47%, respectively. Minimum detectable differences $({\Delta})$ at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 12.62% and 17.63% for $AUC_t,\;and\;C_{max}$, respectively). The powers $(1-{\beta})$ at ${\alpha}=0.05$, ${\Delta}=0.2$ for $AUC_t\;and\;C_{max}$ were above 99.00% and 88.56%, respectively. The 90% confidence intervals were within ${\pm}20%$ (e.g., $-9.96{\sim}4.82$ and $-4.54{\sim}16.09$ for $AUC_t\;and\;C_{max}$, respectively). Two parameters met the criteria of KFDA for bioequivalence, indicating that $Rebamide^{TM}$ tablet is bioequivalent to $Mucosta^{TM}$ tablet.

• Journal of Pharmaceutical Investigation
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• 제34권6호
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• pp.521-527
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• 2004

Cimetidine is a histamine $H_2-receptor$ antagonist, used for the treatment of endoscopically or radiographically comfirmed duodenal ulcer, pathologic GI hypersecretory conditions, and active, benign and gastric ulcer. Simple method for determining cimetidine in human plasma has been developed and validated. The analytical procedure for cimetidine showed a linear relationship in the concentration ranges from $0.05\;to\;5\;{\mu}g/ml$. Coefficient of variance (CV, %) for intraday and interday validation and relative error (RE, %) were less than ${\pm}15%$. Based on this analytical method, the bioequivalence of two cimetidine 400 mg tablets, reference (Tagamet 400 mg) and test drug (Sinil CIMETIDINE 400 mg) was evaluated according to the guidelines set by the Korea Food and Drug Administration (KFDA). Release of cimetidine from the tablets in vitro was tested using KP VIII Apparatus II with various dissolution media (pH 1.2, 4.0, 6.8 buffer solutions and water). Twenty-four healthy volunteers, $21.38{\pm}1.86$ years in age and $68.71{\pm}8.68\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was performed. After oral administration of a tablet containing 400 mg of cimetidine, blood samples were taken at predetermined time intervals and concentrations of cimetidine in plasma were determined using HPLC equipped with UV detector. The dissolution profiles of the two tablet formulations were very similar at all dissolution media. In addition, pharmacokinetic parameters such as $AUC_t$ and $C_{max}$ were calculated and ANOVA was employed for the statistical analysis of parameters. The results were revealed that the differences in $AUC_t$ and $C_{max}$ between the two tablets were 4.17 % and 0.97% respectively. At 90% confidence intervals, the differences in these parameters were also within ${\pm}20%$. All of the above mentioned parameters have met the criteria of KFDA guidelines for bioequivalence, indicating that the test drug tablet (Sinil CIMETIDINE tablet) is bioequivalent to Tagamet 400 mg tablet.

• Biomolecules & Therapeutics
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• 제16권3호
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• pp.255-260
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• 2008

The purpose of this study was to evaluate the bioequivalence of the test (Daewoo Hydrocortisone 10 mg, Daewoo Pharm. Co., Busan, Korea) and reference (Jenapharm Hydrocortisone 10 mg, JayTech Biogen, Seoul, Korea) hydrocortisone tablets. Twenty-four healthy male Korean volunteers were divided into two groups with a randomized $2{\times}2$ cross-over design. In order to suppress the endogenous cortisol secretion, a single oral dose of Dexamethasone (4 mg) was administered 10 hr prior to hydrocortisone administration. Blood samples were withdrawn for 10 hr at the predetermined intervals after a single oral dose of hydrocortisone (20 mg). The serum concentration of hydrocortisone was analyzed by HPLC/UV using a column switching method after liquid-liquid extraction process. The pharmacokinetic parameters ($AUC_{0{\sim}10hr}$, $C_{max}$, and $T_{max}$) of the test and reference hydrocortisone tablets were determined while the secretion of endogenous cortisol was being suppressed. The pharmacokinetic parameters of the test tablet were not statistically different from those of the reference tablet at ex value was 0.05. The 90% confidence intervals for the average ratio (test/reference) of $AUC_{0{\sim}10hr}$ and $C_{max}$ were within the Korea Food and Drug Administration acceptance range of 0.80-1.25 ($0.89{\sim}0.99$ and $0.86{\sim}0.99$ for $AUC_{0{\sim}10hr}$ and $C_{max}$, respectively). Therefore it was concluded that the test tablet, Daewoo Hydrocortisone tablet was bioequivalent to the reference tablet, Jenapharm Hydrocortisone tablet.

• Journal of Pharmaceutical Investigation
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• 제31권3호
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• pp.143-150
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• 2001

Butyrolactone ester of ceftezole (CFZ-BL) was synthesized by esterification of ceftezole (CFZ) with ${\alpha}-bromo-{\gamma}-butyrolactone$. The synthesis was confirmed by spectroscopic analysis. CFZ-BL was more lipophilic than CFZ when the lipophilicity was assessed by partition coefficients between n-octanol and water at various pH. CFZ-BL itself did not show any microbiological activity in vitro, but serums taken after oral administration of CFZ-BL showed substaintial microbiological activity indicating that CFZ-BL is converted to microbiologically active metabolite, probably CFZ, in the body. The conversion was confirmed by in vitro incubation study, in which CFZ-BL was incubated in some body tissues of rabbit. Liver homogenate showed fastest conversion of CFZ-BL among the tissues tested (blood and intestine). Thus, CFZ-BL appeares to be rapidly metabolized in the liver to CFZ following oral administration. The metabolism process appears to be hydrolysis of the ester to CFZ, the parent drug of CFZ-BL. In vivo metabolism of CFZ-BL to CFZ was confirmed by analying CFZ by HPLC. CFZ concentration in the serum samples taken after oral administration of CFZ-BL were higher than those in the serum samples taken after oral administration of equivalent amount of CFZ. Oral bioavailability of CFZ-BL, a prodrug of CFZ, was 1.45-fold higher than that of CFZ in rabbits possibly due to enhanced lipophility and absorption of the prodrug.

• Journal of Pharmaceutical Investigation
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• 제39권5호
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• pp.359-366
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• 2009

In this study, paclitaxel-loaded lipid nanosuspension (PxLN) was prepared and the in vivo profiles after intravenous administration in rats were investigated. We compared the manufacturing processes depending on the temperature: PxLN-H for a hot homogenization process and PxLN-C for solidification of lipid-drug mixtures by liquid nitrogen. Both formulations showed submicron size distribution and the similar drug loading efficiency of about 70%. In vitro release of PxLNs and Taxol$^{(R)}$ performed by a dialysis diffusion method showed similar pattern for PxLN-H and Taxol$^{(R)}$, but the reduced release profile for PxLN-C. PxLN or Taxol$^{(R)}$ was intravenously administered to the rats at a dose of 5 mg/kg as paclitaxel. The drug in blood samples were assayed by the HPLC/MS/MS method. The AUC$_t$ of PxLN-H was 3.4-fold greater than that of Taxol$^{(R)}$. PxLN-H gave higher biodistribution in all tissues than did Taxol$^{(R)}$. In addition, it maintained the higher drug concentration for 12 h. This lipid nanosuspension might be a promising candidate for an alternative formulation for the parenteral delivery of poorly water-soluble paclitaxel.

• 대한지역사회영양학회지
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• 제9권4호
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• pp.483-490
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• 2004

Elevated maternal plasma homocysteine concentrations have been associated with adverse pregnancy outcomes, including birth defects, low birth weight, preeclampsia, spontaneous abortion, placental abruption, and other maternal or fetal complications. The purpose of this study was to assess the maternal plasma homocysteine level during pregnancy and to investigate the relationship between the plasma homocysteine concentrations and pregnancy outcomes. Venous blood samples were drawn from 82 pregnant women who were grouped with gestational age, 1st trimester (n = 26), 2nd trimester (n = 27) and 3rd trimester (n = 29). The concentration of plasma homocysteine was analyzed by HPLC, and pregnancy outcomes including gestational length, maternal weight gain, infant birth weight, and Apgar score were collected with the medical records of the pregnant women. The levels of plasma homocysteine of the pregnant women at the 1st, 2nd, and 3rd trimester were 5.7 $$\pm$ 3.7\mu㏖/L,\;5.6 \pm4.1\mu㏖/L\; and\; 7.0\pm 4.5\mu㏖/L$, respectively, which had not showed any significant difference. The result of this study showed that in case of the pregnant women at the 1st trimester, the maternal plasma homocysteine level of the pregnant women whose gestational length was less than 38 weeks was significantly high (p < 0.01) compared to that of the pregnants whose gestational length was more than 38 weeks. And also, the level of homocysteine of the pregnant women at the 2nd trimester was significantly low when the maternal weight gain was high (p < 0.05). These findings suggest that maternal plasma homocysteine level at early stage of gestation will be a predicter of gestational length and maternal weight gain.

• 한국환경보건학회지
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• 제40권5호
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• pp.407-412
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• 2014

Objectives: The internal dose of ethyl parabens is important in order to evaluate the risk of this chemical. However, there are little PK model data for parabens to apply this. This experiment attempted PK modeling to ascertain PK values. Methods: Twenty mg/kg ethyl paraben was administered orally to Sprague-Dawley rats at the same point in time. The rats were sacrificed at times 0, 15, 30 and minutes, and 1, 2, 4, 8, 12, 24 hours after oral gavage. Blood and urine were collected and pretreated for analysis. Accuracy, precision and LOD (limit of detection) were calculated for this analysis. Ethyl paraben, detected by HPLC-MS, was applied to PK modeling using Berkeley Madonna. Results: This study showed 100.1-103.7% accuracy, 1.4-3.7% precision and a 1.0 ng/mL limit of detection. Orally administered ethyl paraben reached maximum concentration after 30 minutes of dosing in serum and urine of rats. The concentrations were 2,354 ng/mL in serum and 386,000 ng/mL in urine samples. These peak concentrations were excreted after one hour of intubation over 12 hours. For the pharmacokinetic parameters of ethyl paraben revealed using Berkeley Madonna, the absorption rate was 5.539/hour, the excretion rate was 0.048/hour, the half-life was 14.441 hours and AUC was 481,186 ng hour/mL. Conclusion: Orally administered ethyl paraben was absorbed rapidly in rats and excreted in urine. This chemical, ethyl paraben, accumulated in the body but was excreted over 12 hours after dosing.

• 한국임상약학회지
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• 제8권1호
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• pp.19-22
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• 1998

Cefixime is an orally absorbed 3rd generation cephalosporin with a broad spectrum of activity against Gram-positive and Gram-negative bacteria and is highly resistant to $\beta-lactamase$ degradation. This study was carried out to evaluate the bioavailability of a new test drug of cefixime (100 mg/capsule) relative to the reference drug. The bioavailability was conducted on 20 healthy volunteers who received a single dose (400 mg) of the test and the reference drugs in the fasting state, in a randomized balanced 2-way crossover design. After dosing, serial blood samples were collected for a period of 12 hours. Plasma was analyzed for cefixime by a sensitive and validated HPLC assay. The major pharmacokinetic parameters $(AUC_{0-12hr},\;C_{max},\;T_{max})$ were calculated from the plasma concentration-time data of each volunteer. The $AUC_{0-12hr},\;C_{max}\;and\;T_{max}$ of the test drug were $36.91\pm11.85\;{\mu}g{\cdot}hr/ml,\;5.47\pm1.61\;{\mu}g/ml,\;and\;4.00\pm0.65\;hr,$ respectively, and those of the reference drug were $34.08\pm8.81\;{\mu}g{\cdot}hr/ml,\;5.25\pm1.40\;{\mu}g/ml,\;and\;4.20\pm0.62\;hr$, respectively. Mean differences of those parameters were 8.32, 4.29, and $4.76\%$, respectively, and the least significant differences at $\alpha$=0.05 for $AUC_{0-12hr},\;C_{max},\;T_{max}$ were 16.02, 13.78, and $11.76\%$, respectively. In conclusion, the test drug was bioequivalent with the reference drug.

• 동의생리병리학회지
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• 제19권2호
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• pp.459-465
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• 2005

This study was conducted to investigate the application possibility of leaf and stem extract(LSE) extracted from mixture of leaf and stem of ginseng radix (Panax Ginseng C.A. Meyer). We conducted analysis of the ginsenoside content by HPLC. Also we investigate the effects of the LSE on the reduction of serum lipid and improvement of blood parameters in rats fed high fat diet 5 weeks. We examined by analyzing the serum total cholesterol, HDL-cholesterol, LDL-cholesterol, triglyceride and atherogenic index and hematological datas and serum metabolic variables. Sprague-Dawley rat weigh $150\;g\;{\pm}\;15\;g$, were ramdomly assigned to 4 groups, basal diet only(BDG), high fat diet weithout LSE(FDCG), high fat diet and 10% LSE(FD10G), high fat diet and 20% LSE(FD20G). The result of this study were as follow. Hematological datas of 4 groups were same level, which were not significant. The activities of ALP, GOT and LDH level were significantly different. Total cholesterol, LDL-cholesterol, triglyceride contentrations in serum and atherogenic index were remarkably reduced in LSE supplemented groups as compared high fat control groups. These result imply that LSE could be used as possible for decrease of serum lipid concentration.

• 수산해양교육연구
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• 제28권3호
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• pp.692-700
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• 2016

넙치($700{\pm}50g$, $23{\pm}1.5^{\circ}C$) 및 조피볼락($500{\pm}30g$, $23{\pm}1.5^{\circ}C$)에게 Thiamphenicol(TP)을 1일 1회 경구(100 mg/kg BW) 투여한 다음, 경시적(1시간~432시간)으로 혈청 내 TP의 잔류량을 HPLC로써 분석하였다. TP를 어류 혈청에 0.1, 1.0, $10{\mu}g/mL$으로 첨가한 각각의 농도에 대하여 넙치 및 조피볼락에서 TP의 평균 회수율은 77.05~97.23%와 89.96~97.11%로 나타났다. TP의 경구 투여에 따른 넙치와 조피볼락의 체내 약물 혈중농도는 two-compartment model로 조사되었다. TP를 투여 후 넙치 혈청에서 10시간째 $10.08{\mu}g/mL$와 15시간째 $10.06{\mu}g/mL$로 최대값을 보였고, 조피볼락 혈청에서는 15시간째 $8.88{\mu}g/mL$로 최대값을 나타내었다. 넙치와 조피볼락의 혈청에서 TP는 투여 후 432시간째(18일째) 모든 시료에서 검출한계 이하로 검출되지 않았다. TP의 어류 체내 잔류 양상은 넙치와 조피볼락에서 매우 유사하였다. 본 연구에서 얻어진 결과는 넙치와 조피볼락에 TP를 처방하여 치료 계획을 수립할 때 유용하게 활용될 것으로 여겨진다.