• Journal of Pharmaceutical Investigation
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• 제34권3호
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• pp.209-214
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• 2004

A bioequivalence study of $Roxithrin^{TM}$ tablet (Kukje Pharma. Ind. Co., Ltd.) to $Rulid^{TM}$ tablet (Han Dok Pharma. Ind. Co., Ltd.) was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty four healthy male Korean volunteers received each medicine at the roxithromycin dose of 300 mg in a $2{\times}2$ crossover study. There was a one-week wash-out period between the doses. Plasma concentrations of roxithromycin were monitored by a high-performance liquid chromatography for over a period of 36 hours after drug administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 36 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_t$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters indicating that the cross-over design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for $Roxithrin^{TM}/Rulid^{TM}$ were 1.00 - 1.13 and 0.98 - 1.10, respectively. These values were within the acceptable bioequivalence intervals of 0.80 - 1.25. Thus, our study demonstrated the bioequivalence of $Roxithrin^{TM}$ and $Rulid^{TM}$ with respect to the rate and extent of absorption.

• Journal of Pharmaceutical Investigation
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• 제41권3호
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• pp.191-196
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• 2011

In this study simple and sensitive high performance liquid chromatographic method using a commercially available column, was developed and validated for the determination of zolpidem tartrate in human plasma. The developed method with suitable validation was applied to a bioequivalence study of two different kinds of zolpidem tartrate. Two different formulations containing 10 mg of zolpidem tartate (CAS : 99294-93-6) were compared in 24 healthy male volunteers in order to compare the bioavailability and prove the bioequivalence. The study was performed in an open, single dose randomized, 2-sequence, cross-over design in 24 healthy male volunteers with a one-week washout period. Blood samples for pharmacokinetic profiling were drawn at selected times during 12 h. The mean $AUC_{0-12h}$, $C_{max}$, $T_{max}$ and $T_{1/2}$ were $676.6{\pm}223.4$ $ng{\cdot}h{\cdot}mL^{-1}$, $177.4{\pm}34.2$ $ng{\cdot}mL^{-1}$, and $0.8{\pm}0.4$ and $3.5{\pm}2.1$, respectively, for the test formulations, and $640.7{\pm}186.6$ $ng{\cdot}h{\cdot}mL^{-1}$, $193.0{\pm}64.5$ $ng{\cdot}mL^{-1}$, and $0.9{\pm}0.4$ and $2.7{\pm}0.9$, respectively, for the reference formulation. Both primary target parameters $AUC_{0-12h}$ and $C_{max}$ were log-transformed and tested parametrically by analysis of variance (ANOVA). 90% confidence intervals of $AUC_{0-12h}$ and $C_{max}$ were in the range of acceptable limits of bioequivalence (80-125%). Based on these results, the two formulations of zolpidem tartate are considered to be bioequivalent.

• Journal of Pharmaceutical Investigation
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• 제38권6호
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• pp.421-427
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• 2008

The purpose of the present study was to evaluate the bioequivalence of two etodolac capsules, Kuhnillodin capsule (Kuhnil. Co., Ltd., Seoul, Korea) as reference drug and Etodin capsule (Myungmun Pharm. Co., Ltd., Seoul, Korea) as test drug, according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-three healthy male Korean volunteers received one capsule at the dose of 200 mg etodolac in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Plasma concentrations of etodolac were monitored by a high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) for over a period of 24 hr after the administration. $AUC_{0-24\;hr}$ was calculated by the linear trapezoidal rule method. $C_{max}$ and $T_{max}$ were compiled from the plasma concentration-time data. Analysis of variance (ANOVA) was carried out using logarithmically transformed $AUC_{0-24\;hr}$ and $C_{max}$. The 90% confidence intervals of the $AUC_{0-24\;hr}$ ratio and the $C_{max}$ ratio for Etodin/Kuhnillodin were $\log\;0.97{\sim}\log\;1.08$ and $\log\;0.89{\sim}\log\;1.19$, respectively. These values were within the acceptable bioequivalence intervals of $\log\;0.80{\sim}\log\;1.25$. Thus, our study demonstrated that Etodin was bioeqiovalent to Kuhnillodin preparation when the rate and extent of absorption between two preparations were compared.

• Journal of Applied Biological Chemistry
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• 제63권3호
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• pp.267-274
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• 2020

상추 중 살균제 mandipropamid 및 살충제 thiamethoxam의 생산단계 잔류허용기준(PHRLs)를 추정하기 위해 3곳의 상추 시설재배지에서 두 약제의 경시적 잔류량 감소특성을 조사하였다. 상추 중 농약 잔류량은 HPLC-PDA 또는 UVD를 이용하여 분석하였으며 우수한 회수율 및 변이값을 보여 분석의 유효성을 확보하였다. 농약안전사용기준에 따라 약제살포 권고량을 살포한 후 살포 후 수확일(PHI)을 포함한 10일 동안 출하시기에 적합한 개체를 채취하여 잔류량을 분석하였다. 포장별 초기 평균 잔류량은 mandipropamid 6.68-17.87 mg/kg, thiamethoxam 4.96-8.31 mg/kg이었고 10일 경과 후 각각 초기잔류량의 16-54 및 14-44% 수준으로 감소하였다. Thiamethoxam의 대사산물인 clothianidin은 <0.02-0.37 mg/kg으로 검출되었다. 상추 중 두 약제의 잔류량은 단순 1차 감쇄반응처럼 감소하였으며 포장구분없이 일자별 잔류량 회귀식을 산출한 결과, 평균 감소상수 및 생물학적 반감기는 mandipropamid의 경우 -0.1060 및 6.5일이었고 thiamethoxam은 -0.1236 및 5.6일이었다. 상추 잔류량 감소상수의 95% 신뢰구간 상한치는 mandipropamid -0.0746 및 thiamethoxam -0.1091이었으며, 출하 10일 및 5일 전 PHRLs은 mandipropamid의 경우 63.24 및 43.56 mg/kg, thiamethoxam은 44.66 및 25.88 mg/kg으로 산출되었다. 본 연구결과는 농가에서 농작물 출하시기를 조절하는데 활용될 수 있으며 농가의 소득 안정화에 기여할 것으로 판단된다.

• 대한의용생체공학회:의공학회지
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• 제32권3호
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• pp.237-244
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• 2011

In this paper, a feature-based registration technique is proposed for pre-contrast and post-contrast lung CT images. It utilizes three dimensional(3-D) features with their descriptors and estimates feature correspondences by nearest neighborhood matching in the feature space. We design a transformation model between the input image pairs using a free form deformation(FFD) which is based on B-splines. Registration is achieved by minimizing an energy function incorporating the smoothness of FFD and the correspondence information through a non-linear gradient conjugate method. To deal with outliers in feature matching, our energy model integrates a robust estimator which discards outliers effectively by iteratively reducing a radius of confidence in the minimization process. Performance evaluation was carried out in terms of accuracy and efficiency using seven pairs of lung CT images of clinical practice. For a quantitative assessment, a radiologist specialized in thorax manually placed landmarks on each CT image pair. In comparative evaluation to a conventional feature-based registration method, our algorithm showed improved performances in both accuracy and efficiency.

• 융합정보논문지
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• 제10권11호
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• pp.340-350
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• 2020

본 연구는 병원행정직에 적합한 직업 및 직무가치와 자신의 능력에 대한 개인의 주관적 인식인 포괄적 전문직업성 측정도구를 제시하고자 실시하였다. 연구는 부산·경남 지역 종합병원 및 병원에 근무하는 행정직 종사자들을 대상으로, 선행연구들에서 사용된 개인의 심리적·태도적 속성과 관련된 측정도구를 이용하였다. 분석은 직업 및 직무수행과 관련된 심리적·태도적 속성 측정내용의 타당성과 내적일관성을 확인하기 위하여 요인분석과 신뢰도 분석을 실시하였다. 분석결과, 타당성과 내적일관성이 확보된 5개 성분은 전체 신뢰도가 94.4%로 병원행정직 종사자들의 포괄적 전문직업성 측정도구로 매우 타당하다는 결론을 얻었다. 따라서 각 성분은 측정내용의 공통성과 명확한 의미전달이 될 수 있도록 직무수행 자신감, 보수 적절성, 직무 자부심, 업무목표 달성 능력, 업무수행 자율성으로 정의하였다. 현대적 관점에서의 전문직업성은 전통적 전문직업성 보다 넓은 개념으로 자격 및 면허 여부와 관계없이 직업 및 직무가치와 자신의 능력에 대한 개인의 주관적 인식 등에 대한 가치를 포함하고 있다. 따라서 본 연구에서 제시된 포괄적 전문직업성 측정도구는 병원행정직 종사자들의 직업 및 직무수행과 관련된 심리적·태도적 속성을 측정하는데 매우 적합하고 유용하게 활용될 수 있을 것으로 사료된다.

• 한국임상약학회지
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• 제8권2호
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• pp.107-112
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• 1998

Lovastatin is a lipid lowering agent for the treatment of hypercholesterolemia and belongs to a new class of pharmacologic compounds called the 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors. By competitively inhibiting HMG CoA reductase, lovastatin disrupts the biosynthesis of cholesterol in hepatic and peripheral cells and increases the synthesis of high-density-lipoprotein HDL) receptors. Following oral administration, the lactone ring of lovastatin is hydrolysed to the active inhibitor of HMG CoA reductase, lovastatin acid. Lovastatin is known to have poor oral absorption and wide individual variation. In this study, bioequivalence test of two lovastatin formulations, the test drug ($Lovaload^{TM}$, Chong Kun Dang Pharmaceutical Co.) and the reference drug ($Mevacor^{TM}$, Chung Wae Pharmaceutical Co.) were conducted according to the guidelines of Korea Food and Drug Administration (KFDA). A total of 18 healthy male volunteers, $31.90\pm3.60$ years old and $72.17\;7.88$ kg of body weight in average, were evaluated in a randomized crossover manner with a 2-week washout period. Concentrations of lovastatin acid in plasma were measured upto 12 hours following a single oral administration of eight tablets (20 mg of lovastatin per tablet) by high-performance liquid chromatography with UV detection at 238 nm. The area under the concentration-vs-time curve from 0 to 12 hours $(AUC_{0-12h})$ was calculated by the trapezoidal summation method. The statistical analysis showed that there are no significant differences in $AUC_{0-12h),\;C_{max}\;and\;T_{max}$ between the two formulations ($6.72\%,\;1.52\%,\;and\;0.88\$, respectively). The least significant differences between the formulations at $\alpha$=0.05 were less than $20\%\;(11.65\%,\;19.73\%,\;and\;14.81\%\;for\;AUC_{0-12h},\;C_{max}\;and\;T_{max}$, respectively). The $90\%$ confidence intervals for these parameters were also within $\pm20\%\;(-1.50{\leq}{\delta}{\leq}15.00$, $-12.50{\leq}{\delta}{\leq}15.50,\;and\;-9.64{\leq}{\delta]{\leq}11.40{\leq}\;for\;\;AUC_{0-12h}$ ,$C_{max}\;and\;T_{max}$, respectively). In conclusion, the new generic product $Lovaload^{TM}$ was proven to be bioequivalent with the reference drug.

• 한국임상약학회지
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• 제10권1호
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• pp.13-18
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• 2000

The bioequivalence of two clarithromycin tablets, the $Klaricid^{TM}$ (Ciba-Geigy Korea Ltd.) and the $Pylocin^{TM}$ (Kyungdong Pharmaceutical Co., Ltd.), was evaluated according to the Korean Guidelines for Bioequivalence Test (KGBT 1998). Sixteen healthy male volunteers ($20\sim26$ years old) were randomly divided into two groups and a randomized $2\times2$ cross-over study was employed. After one tablet containing 250 mg of clarithromycin was orally administered, blood sample was taken at predetermined time intervals, and the concentrations of clarithromycin in serum were determined using high-performance liquid chromatographic method with electrochemical detector. The pharmaco-kinetic parameters (area under the concentration-time curve: $AUC_t$, maximum concentration; $C_{max}$ and time to maximum concentration; $T_{max}$) were calculated and analysis of variance (ANOVA) was utilized for the statistical analysis of parameters. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between two tablets based on $Klaricid^{TM}$ tablet were $-0.22\%,\;-0.48\%\;and\;-1.63\%$, respectively. The powers $(1-\beta)\;for\;AUC_t,\;C_{max}\;and\;T_{max}\;were\;99.07\%,\;88.15\%\;and\;99.99\%$, respectively. Detectable differences $(\Delta)\;and\;90\%$ confidence intervals ($\alpha$=0.10) were all less than $\pm20\%$ All the parameters above met the criteria of KGBT 1998, indicating that $Pylocin^{TM}$ tablet is bioequivalent to $Klaricid^{TM}$ tablet.

• Journal of Gastric Cancer
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• 제17권2호
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• pp.132-144
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• 2017

Purpose: To identify baseline prognostic factors for survival in patients with disease progression, during or after chemotherapy for the treatment of advanced gastric or gastroesophageal junction (GEJ) cancer. Materials and Methods: We pooled data from patients randomized between 2009 and 2012 in 2 phase III, global double-blind studies of ramucirumab for the treatment of advanced gastric or GEJ adenocarcinoma following disease progression on first-line platinum- and/or fluoropyrimidine-containing therapy (REGARD and RAINBOW). Forty-one key baseline clinical and laboratory factors common in both studies were examined. Model building started with covariate screening using univariate Cox models (significance level=0.05). A stepwise multivariable Cox model identified the final prognostic factors (entry+exit significance level=0.01). Cox models were stratified by treatment and geographic region. The process was repeated to identify baseline prognostic quality of life (QoL) parameters. Results: Of 1,020 randomized patients, 953 (93%) patients without any missing covariates were included in the analysis. We identified 12 independent prognostic factors of poor survival: 1) peritoneal metastases; 2) Eastern Cooperative Oncology Group (ECOG) performance score 1; 3) the presence of a primary tumor; 4) time to progression since prior therapy <6 months; 5) poor/unknown tumor differentiation; abnormally low blood levels of 6) albumin, 7) sodium, and/or 8) lymphocytes; and abnormally high blood levels of 9) neutrophils, 10) aspartate aminotransferase (AST), 11) alkaline phosphatase (ALP), and/or 12) lactate dehydrogenase (LDH). Factors were used to devise a 4-tier prognostic index (median overall survival [OS] by risk [months]: high=3.4, moderate=6.4, medium=9.9, and low=14.5; Harrell's C-index=0.66; 95% confidence interval [CI], 0.64-0.68). Addition of QoL to the model identified patient-reported appetite loss as an independent prognostic factor. Conclusions: The identified prognostic factors and the reported prognostic index may help clinical decision-making, patient stratification, and planning of future clinical studies.

• 한국정보통신학회논문지
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• 제14권12호
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• pp.2783-2790
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• 2010

본 연구에서는 무선 랜 표준안인 802.11n에서 채널 부호화 알고리즘으로 채택된 LDPC부호의 복호 알고리즘의 저복잡도에 대해 연구를 하였다. 샤논의 한계에 근접하기 위해서는 큰 블록 사이즈의 LDPC 부호어 길이와 많은 반복횟수를 요구한다. 이는 많은 계산량을 요구하며, 그리고 이에 따른 전력 소비량(power consumption)을 야기 시키므로 본 논문에서는 세 가지 형태의 저복잡도 LDPC 복호 알고리즘을 제시한다. 첫째로 큰 블록 사이즈와 많은 반복 횟수는 많은 계산량과 전력 소모량을 요구하므로 성능 손실 없이 반복횟수를 줄일 수 있는 부분 병렬 방법을 이용한 복호 알고리즘, 둘째로 early stop 알고리즘에 대해 연구 하였고, 셋째로 비트 노드 계산과 체크 노드 계산 시 일정한 신뢰도 값보다 크면 다음 반복 시 계산을 하지 않는 early detection 알고리즘에 대해 연구 하였다. 위 세가지 알고리즘을 적용하여 FPGA 칩에 구현한 결과 N=648, R=1/2일 때, 복호 속도는 알고리즘을 적용하지 않았을 때 보다 거의 두배에 가까운 110Mbps이고, 약 45%의 디바이스 사용량이 감소하였다.