• Journal of Pharmaceutical Investigation
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• 제40권2호
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• pp.125-131
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• 2010

A bioequivalence study of LANIDIEM$^{(R)}$ tablet 4 mg (Samil. Co., Ltd.) to Vaxar$^{(R)}$ tablet 4 mg (GlaxoSmithKline Co., Ltd.) was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Forty healthy male Korean volunteers were enrolled in the study and thirty six volunteers completed the study according to the protocol. Thirty six volunteers received each medicine at the lacidipine dose of 4 mg in a $2{\times}2$ crossover study. There was one week wash-out period between the doses. Plasma concentrations of lacidipine were monitored by a high performance liquid chromatography - tandem mass spectrometry (LC-MS/MS) for over a period of 24 hours after drug administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 24 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 crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for LANIDIEM$^{(R)}$/Vaxar$^{(R)}$ were log 0.8102~log 1.0417 and log 0.8493~log 1.1439, respectively. These values were within the acceptable bioequivalence intervals of log 0.80~log 1.25. Thus, our study demonstrated the bioequivalence of LANIDIEM$^{(R)}$ tablet 4 mg and Vaxar$^{(R)}$ tablet 4 mg with respect to the rate and extent of absorption.

• 한국식품위생안전성학회지
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• 제25권1호
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• pp.65-72
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• 2010

총아플라톡신의 분석을 위하여 대상 시료로부터 추출된 용액을 면역친화성칼럼 (immunoaffinity column)을 이용하여 정제하고 트리플루오로초산(TFA, trifluoroacetic acid) 유도체법과 광유도체화 형태인 PHRED (Photochemical reactor enhanced detection) 유도체 법을 비교 검토하여 분석하였다. 결과적으로 재현성 및 편리성은 PHRED유도체법이 우수하였으나 분리도 및 검출한계는 TFA유도체법이 우수하였다. 확립된 시험법은 아플라톡신 B1, B2, G1은 80% 이상, G2는 70% 이상의 회수율을 보였고, 아플라톡신 B1, B2, G1 및 G2 각각 0.05, 0.05, 0.2 및 $0.1\;{\mu}g/kg$의 검출한계를 나타내었다. 확립된 시험법으로 향신료 및 건조과실류 중 총 아플라톡선에 대한 실태 조사를 위하여 향신료 10종 179건 및 건조과실류 9종 137건 총 316건을 분석하였다. 그 결과, 건조과실류 건망고 등 9종 137건 중 27건(19.7%)에서 아플라톡신이 소량 검출되었으며, 건조향신료 육구두 등 10종 179건 중 87건 (48.6%)에서 아플라톡선이 검출되었다.

• 한국식품과학회지
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• 제43권3호
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• pp.263-270
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• 2011

본 연구는 인삼 및 인삼 가공품에 대한 합리적인 농약잔류허용기준 설정과 인삼 및 가공품 중 농약의 잔류성을 규명하고 이를 토대로 인삼 가공단계별 농약의 감소계수와 가공계수를 산출하고자 수행되었다. 시험농약은 difenoconazole로 6년근 인삼포 2곳(강원도 원주, 경기도 이천)에 농약사용기준에 따라 살포한 후 수삼을 수확하여 건삼, 홍삼, 인삼 농축액 및 홍삼 농축액 시료로 가공하였다. 시험결과 difenoconazole의 잔류량은 원주, 이천수삼에서 모두 LOQ(0.02 mg/kg) 미만, 건삼은 각각 0.04 mg/kg, 0.10 mg/kg, 홍삼은 각각 LOQ(0.04 mg/kg) 미만, 0.08 mg/kg, 인삼 알코올 농축액은 각각 0.07, 0.36 mg/kg, 인삼 물 농축액은 모두 LOQ(0.04 mg/kg) 미만, 홍삼 알코올 농축액은 각각 0.08 mg/kg, 0.18 mg/kg, 홍삼 물 농축액은 모두 LOQ(0.04 mg/kg) 미만으로 모두 농약잔류허용기준(MRL) 이하였다. Difenoconazole의 가공계수는 건삼 3.55, 홍삼 3.17, 인삼 알코올 농축액 10.78, 인삼 물 농축액 2.00, 홍삼 알코올 농축액 6.45, 홍삼 물 농축액 2.00으로 산출되었으며, 감소계수는 건삼 1.09, 홍삼 1.02, 인삼 알코올 농축액 3.74, 인삼 물 농축액 0.73, 홍삼 알코올 농축액 2.42, 홍삼 물 농축액 0.74였다.

• 대한화장품학회지
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• 제41권3호
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• pp.219-227
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• 2015

본 연구에서는 시중에서 유통 중인 어린이용 화장품 총 125건(n = 125)을 대상으로 하여 파라벤 6종과 벤질알콜, 페녹시에탄올, 소르빈산, 벤조산 등 10종의 보존제에 대한 혼합 사용실태와 함량을 HPLC를 이용하여 조사하였다. 유형별 보존제 검출률은 세정제 63%, 크림류 48%, 자외선차단제 46%, 로션류 38%, 오일이 13%의 순으로 검출되어 총 125건 중 63건(50%)의 제품에서 1종류 이상의 보존제를 사용하고 있는 것으로 조사되었다. 보존제별 검출범위는 페녹시에탄올 0.01 ~ 0.91% (n = 35), 벤조산 0.01 ~ 0.48% (n = 28), 벤질알콜 0.01 ~ 0.78% (n = 9), 소르빈산 0.01 ~ 0.11% (n = 3)였으며, 파라벤류 중 메틸 파라벤과 프로필 파라벤은 0.04 ~ 0.21% (n = 8)와 0.02 ~ 0.09% (n = 8)의 검출범위를 보였고, 에틸 파라벤은 1개 제품에서 0.04%로 모두 배합한도 이내로 검출되었다. 조사결과 어린이용 화장품에서는 파라벤류 보다 페녹시에탄올과 벤조산의 사용 빈도가 높았으며 검출된 파라벤류 중에서는 메틸 파라벤과 프로필 파라벤이 주로 혼합 사용되는 것으로 나타났다.

• 한국약용작물학회지
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• 제16권6호
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• pp.390-396
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• 2008

The aim of this work is to assess the safety of fungicide tolclofos-methyl, difenoconazole and azoxystrobin in ginseng sprayed by safe use guideline. When tolclofos-methyl was sprayed on ginseng by safe use guideline, the residue amounts (MRL) of it in ginseng was 0.13 mg/kg which is below than 0.3 mg/kg, maximum residue limit established by Korea Food & Drug Administration (KFDA). The residue amounts of ginseng parts, head part was 0.37 mg/kg and main body part was 0.13 mg/kg. In case of difenoconazole, the residue amounts in ginseng was 0.81 mg/kg. which was exceed the MRL, 0.2 mg/kg. By the analyze results of ginseng part, the residues of head and main body part were 3.01 and 0.40 mg/kg, respectively. In experiment of vinyl mulching, the residue amount of difenoconazole in ginseng was 0.05 mg/kg. The residue amounts of azoxystrobin in ginseng sprayed by safe use guideline was 0.14 mg/kg. This residue was not exceed the MRL 0.5 mg/kg. The residue amounts by ginseng parts was 0.51 mg/kg for head part and 0.28 mg/kg for main body part. In case of vinyl mulching, the residue amount of azoxystrobin was 0.02 mg/kg.

• Journal of Pharmaceutical Investigation
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• 제36권5호
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• pp.331-338
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• 2006

A rapid, selective and sensitive reverse-phase HPLC methods for the determination of atenolol and chlorthalidone in human serum and whole blood were validated, and applied to the pharmacokinetic study of atenolol and chlorthalidone combination therapy. Atenolol and an internal standard, pindolol, were extracted from human serum by liquid-liquid extraction, and analyzed on a $\mu$-Bondapak C18 $10-{\mu}$ column in a mobile phase of methanol-0.01 M potassium dihydrogenphosphate(30:70, v/v, adjusted to pH 3.5) and fluorescence detection(emission: 300 nm, excitation: 224 nm). Chlorthalidone and an internal standard, probenecid, were extracted form human whole blood by liquid-liquid extraction, and analyzed on a Luna C18 $5-{\mu}$ column in a mobile phase of acetonitrile containing 77% 0.01 M sodium acetate and UV detection at 214 nm. These analysis were performed at three different laboratories using the same quality control(QC) samples. The chromatograms showed good resolution, sensitivity, and no interference by human serum and whole blood, respectively. The methods showed linear responses over a concentration range of 10-1,000 ng/mL for atenolol and 0.05-20 ${\mu}g/mL$ for chlorthalidone, with correlation coefficients of greater than 0.999 at all the three laboratories. Intra- and inter-day assay precision and accuracy fulfilled international requirements. Stability studies(freeze-thaw, short-, long-term, extracted sample and stock solution) showed that atenolol and chlorthalidone were stable. The lower limit of quantitation of atenolol and chlorthalidone were 10 ng/mL and 0.05 ${\mu}g/mL$, respectively, which was sensitive enough for pharmacokinetic studies. These methods were applied to the pharmacokinetic study of atenolol and chlorthalidone in human volunteers following a single oral administration of Hyundai $Tenoretic^{\circledR}$ tablet(atenolol 50 mg and chlorthalidone 12.5 mg) at three different laboratories.

• 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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• 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.

• 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.

• Journal of Radiation Protection and Research
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• 제30권4호
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• pp.175-183
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• 2005

2002년 기준으로 국내 52733명의 방사선 작업종사자에 대해 5개 대분류와 28개의 세분류 카테고리로 나눈 직업군별 연간 피폭선량의 분포를 분석하였다. 진단용 X선 분야(치과용 포함) 종사자의 선량 통계는 식품의약품안전청이 제공하였으며 기타 종사자의 선량자료는 한국방사성동위원소협회가 제공하였다. 직업군에 따른 선량준위별, 연령별 성별 종사자수와 연간 평균선량을 분석한 결과 거의 80% 정도의 종사자들이 연간 1.2mSv 이하로 피폭하는 것으로 나타났다. 방사선작업 종사자의 총 집단선량은 66.4man-Sv로 나타났고 평균 선량은 1.26mSv였다. 직업군별로는 체내 핵의학 분야와 비 파괴검사 분야 종사자가 다른 분야에 비해 평균선량이 현저히 높게 나타났다. 진단용 X선 분야 종사자에게서 연간 20mSv 이상 피폭자 수가 상당하여 이에 대한 추가 분석이 필요한 것으로 나타났다. 16기의 원자력발전소 작업종사자 중에는 20mSv를 초과하는 종사자가 한명도 없는 것으로 나타났다. 연령별로 30대 종사자 수가 가장 많았고 20대 종사자의 선량이 상대적으로 높았다. 여성이 전체 작업종사자의 20%정도를 차지하고 있었으며 평균 피폭선량은 남성의 반 정도인 것으로 나타났다.