• Biomolecules & Therapeutics
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• 제7권1호
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• pp.59-65
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• 1999

A bioequivalence study of the Dong Wha Cisapril tablets(Dong Wha Pharm. Ind. Co., Ltd.) to the Prepulsid tablets(Janssen Korea Ltd.), formulations of cisapride, was conducted. Twenty four healthy Korean male subjects received each formulation at the dose of 5 mg as cisapride in a 2$\times$2 crossover study. There was a 1-week washout period between the doses. Plasma concentrations of cisapride were monitored by an LC/MS method for over a period of 36 h after each administration. AUC(area under the plasma concentration- time curve from time zero to infinity) was calculated by the linear trapezoidal and extrapolation method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed that there are no differences in AUC, $C_{max}$ and $T_{max}$ between the formulations. The apparent differences between the formulations in these parameters were all far less than 20% (i.e., 6.8, -6.6 and 1.8% for AUC, $C_{max}$ and $T_{max}$, respectively). Minimum detectable differences(%) at $\alpha$=0.05 and 1-$\beta$=0.8 were all less than 20% in these parameters between the formulations (i.e., 16.5, 11.4 and 16.4% for AUC, $C_{max}$ and $T_{max}$, respectively). The 90% confidence intervals for these parameters were also within 20% (i.e., -2.9~ 16.4, -13.2~0.1 and -7.8~ 11.4% for AUC, $C_{max}$ and $T_{max}$, respectively). These results satisfy the bioequivalence criteria of the Korea Food and Drug Administration (KFDA) guidelines (No. 98-51). Therefore, these results indicate that the two formulations of cisapride are bioequivalent and, thus, may be prescribed interchangeably.hangeably.y.hangeably.

• Biomolecules & Therapeutics
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• 제10권4호
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• pp.303-308
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• 2002

A bioequivalence study of Shin II Cefadroxil capsule (Shin II Pharm. Co. Ltd.) to Duricef capsule(Bo Ryung Pharm. Co. Ltd.), each containing 500 mg of cefadroxil, was conducted. Twenty three healthy Korean male subjects administered each formulation at the dose of 1 capsule (500 mg as cefadroxil) in 2 $\times$ 2 cross-over study. There was a I-week washout period between the doses. Plasma concentrations of cefadroxil were monitored for a period of 8 hr after each administration by an LC/UV method. Area under the plasma concentration-time curve up to 8 hr ($AUC_t$) was calculated by a linear trapezoidal method. $C_{max}$ was compiled from the plasma drug concentration-time data. ANOVA test was conducted for logarithmically transformed $AUC_t$ and $C_{max}$ The results showed that there are no significant differences in $AUC_t$ and $C_{max}$ between the two formulations: The differences between d1e formulations in these log transformed parameters were all for less than 20% (i.e., －0.57%, 3.84% for $AUC_t$ and $C_{max}$, respectively). The 90% confidence intervals for the log transformed data were within the acceptance range of log 0.8 to log 1.25 (i.e., log 0.94~log 1.04 and log 0.95~log 1.10 for $AUC_t$ and $C_{max}$, respectively). Based on d1e bioequivalence criteria of KFDA guidelines, the two formulations of cefadroxil were concluded to be bioequivalent.

• 한국의학물리학회지:의학물리
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• 제19권4호
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• pp.276-284
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• 2008

전 세계적으로 컴퓨터 단층 촬영 장치(Computed Tomography, CT)의 임상 적용이 환자의 질병의 조기 진단에 매우 중요하게 사용되고 있으며 사용 빈도 또한 매년 급증하고 있다. 새로운 종류의 CT 장치들이 병변을 조기 진단하기 위하여 개발되고 있다. 이 방사선 발생 장치에 의한 환자나 작업 종사자들의 방사선 피폭이 불가피 할 수도 있다. 국내에서는 CT 장치에 대한 구체적인 방사선 방어나 방사선 시설에 대한 구체적인 규정이 확립되어 있지 않다. 본 논문에서는 국내에서의 CT 사용시설에 대한 방사선 방어 시설과 사용 기준에 대한 규정 마련에 토대를 이루기 위하여 외국에서의 CT 장비에 대한 방사선 방어 및 방사선 차폐에 대한 규정을 조사하였다. 조사방법으로는 구글 검색을 이용한 특정 키워드 검색과 방사선 관련 업무를 수행하는 특정 웹사이트를 직접 검색하는 방법을 사용하였다. 검색결과 캐나다, 미국, 영국 등의 국가에서 국가의 실정에 맞는 가이드라인을 사용하고 있었으나, 아직 이중 에너지 CT에 대한 가이드라인은 없는 것으로 나타났다. 한국에서도 국내 실정에 적합한 CT 장비에서의 방사선 방어, 차폐, 환자나 작업종사자 및 일반인에 대한 방사선 피폭에 대한 가이드라인의 설정이 필요하다고 생각된다.

• Journal of Pharmaceutical Investigation
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• 제35권3호
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• pp.179-185
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• 2005

Acebrophylline is a compound produced by salifying ambroxol with theophylline-7 -acetic acid. After acebrophylline administration, the salt splits into these two components which feature a peculiar pharmacokinetic behavior, an adequate ambroxol and a low theophylline-7-acetic acid serum levels. The purpose of the present study was to evaluate the bioequivalence of two acebrophylline capsules, Surfolase (Hyundai Pharm. lnd. Co., Ltd.) and Burophil (Kuhnil Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of ambroxol from the two acebrophylline formulations in vitro was tested using KP VIII Apparatus II method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty eight healthy male subjects, $23.25{\pm}1.43$ years in age and $64.82{\pm}6.77$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After two capsules containing 100 mg as acebrophylline were orally administered, blood was taken at predetermined time intervals and the concentrations of ambroxol in serum were determined using HPLC with electrochemical detector (ECD). The dissolution profiles of two formulations were similar at all dissolution media. In addition, 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 using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug Surfolase, were -1.64, -3.33 and -0.92% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 $(e.g., \;log\;0.93{\sim}log\;1.05\;and\;log\;0.88{\sim}log\;1.05$ for $AUC_t$, and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Burophil capsule was bioequivalent to Surfolase capsule.

• Journal of Pharmaceutical Investigation
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• 제36권3호
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• pp.209-215
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• 2006

Zaltoprofen, (2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid) is an NSAID with powerful anti-inflammatory effects as well as an analgesic action on inflammatory pain. The purpose of the present study was to evaluate the bioequivalence of two zaltoprofen tablets, $Soleton^{\circledR}$ (CJ Corp.) and SCD Zaltoprofen (Samchundang Pharmaceutical Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of zaltoprofen from the two zatoprofen formulations in vitro was tested using KP Vlll Apparatus ll method with various dissolution media. Twenty six healthy male subjects, $23.2{\pm}2.26$ years in age and$64.7{\pm}8.08$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single tablet containing 80 mg as zaltoprofen was orally administered, blood samples were taken at predetermined time intervals and the concentrations of zaltoprofen in serum were determined using HPLC with UV detector. The dissolution profiles of two formulations were similar in all tested dissolution media. 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 using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Soleton^{\circledR}$ were 6.33, 5.91 and 17.7% for $AUC_t$, $C_{max}$ and untransformed $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g.,log $1.01{\sim}1og\;1.11$ and log $0.928{\sim}1og\;1.18$ for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating SCD Zaltoprofen tablet was bioequivalent to $Soleton^{\circledR}$ tablet.

• 한국방사선학회논문지
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• 제10권7호
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• pp.477-482
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• 2016

유방촬영검사(Mammography)에서 선량지표를 분석하여 한국식품의약품안전처(Korea Food & Drug Administ ration)에서 제시하는 가이드라인과 비교분석하여 의료방사선의 관리가 잘 이루어지고 있는지 파악하고자 하였다. 방법으로는 유방촬영검사를 시행한 후 의료영상저장정보시스템(Picture Archiving Communication System, PACS)으로 전송되어진 선량 보고서(dose report)와 의료전자차트(Electronic Medical Record, EMR)를 참고하여 양쪽 유방 상하방향촬영(cranio-caudal, CC), 내외 사방향 촬영(medio-lateral oblique, MLO)검사에서 관전압(kVp), 조사시간(exposure time), 관전류량(mAs), 유방압박두께(compressed breast thickness), 평균유선선량(average glandular dose), 체질량지수(Body Mass Index, BMI)를 분류하여 분석하였다. 결과적으로 연령별에 따른 검사부위 CC, MLO에서 유방압박두께는 50-59세에서 45.6 mm, 49.6 mm로 가장 두껍게 나타났으며 전체적인 평균유방압박두께는 CC에서 44.2 mm, MLO 48.9 mm로 MLO가 4.7 mm 더 두껍게 나타났다. 평균유선선량은 CC에서 1.05 mGy, MLO에서 1.14 mGy로 CC보다 MLO에서 0.09 mGy가 더 높게 나타났으며 유방압박두께가 10 mm 증가할수록 CC와 MLO에서는 0.15 mGy, 0.17 mGy가 증가하는 것으로 나타났다. 한국식품의약품안전처에서 제시하는 유방 CC에서 1매 촬영 시 환자가 받는 평균유선선량 1.16 mGy 평가와 비교했을 시 1.05 mGy로 나타났으나 60 mm이상에서는 1.30 mGy로 초과하는 것으로 나타났다. 또한 유방압박두께가 높을수록 체질량지수가 높게 나타났으며 체질량지수에 따른 비만기준 25이상인 경우는 유방압박두께가 50 mm 이상일 경우에 비만인 것으로 나타났다.

• Journal of Pharmaceutical Investigation
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• 제31권4호
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• pp.289-295
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• 2001

Carvedilol is an antihypertensive and antianginal compound that combines nonselective beta-adrenoceptor blocking and vasodilation properties and is devoid of intrinsic sympathomimetic activity. The purpose of the present study was to evaluate the bioequivalence of two carvedilol tablets, $Dilatrend^{TM}$ (Chong Kun Dang Pharmaceutical Co., Ltd.) and $Carvelol^{TM}$ (Dae Won Pharmaceutical Co., Ltd.), according to the prior and revised guidelines of Korea Food and Drug Administration (KFDA). The carvedilol release from the two carvedilol tablets in vitro was tested using KP VII Apparatus II method with various different kinds of dissolution media (pH 1.2, 4.0, 6.8 buffer solution, water and blend of PSB80 into water). Eighteen normal male volunteers, $24.22{\pm}1.86$ years in age and $64.81{\pm}4.56\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 25 mg of carvedilol was orally administered, blood was taken at predetermined time intervals and the concentrations of carvedilol in serum were determined using HPLC method with fluorescence detector. The dissolution profiles of two carvedilol tablets were very similar at all 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 using non-transformed and logarithmically transformed $AUC_t$ and $C_{max}$. The results showed that the differences in $AUC_t$, $C_{max}$ and $T_{max}$ between two tablets based on the $Dilatrend^{TM}$ were 2.23%, -2.00% and 0.00%, respectively. Minimum detectable differences $({\Delta})$ at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 13.55% and 17.61% for $AUC_t$ and $C_{max}$, respectively). The powers $(l-{\beta})$ at ${\alpha}=0.05$, ${\Delta}=0.2$ for $AUC_t$ and $C_{max}$ were 98.08% and 88.81%, respectively. The 90% confidence intervals were within ${\pm}20%$ (e.g., $-5.69{\sim}10.16$ and $-12.30{\sim}8.30$ for $AUC_t$ and $C_{max}$, respectively). There were no sequence effect between two tablets in logarithmically transformed $AUC_t$ and $C_{max}$. The 90% confidence intervals using logarithmically transformed were within the acceptance range of log(0.8) to log(1.25) (e.g., $0.95{\sim}1.11$ and $0.89{\sim}1.09$ for $AUC_t$ and $C_{max}$, respectively). Two parameters met the criteria of prior and revised KFDA guideline for bioequivalence, indicating that $Carvelol^{TM}$ tablet is bioequivalent to $Dilatrend^{TM}$ tablet.

• Journal of Pharmaceutical Investigation
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• 제39권3호
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• pp.207-216
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• 2009

Fluconazole is used as an orally administrated antifungal drug for the treatment of tinea corporis, candidiasis including skin mycotic pneumonia infections. The dosage of fluconazole varies with indication ranging from 50 mg/day to 400 mg/day. The fluconazole capsule 50 mg (3 capsules daily) is already available in Korean market. To improve the patient compliance, a fluconazole tablet 150 mg (once a day administration) was developed recently. The purpose of this study was to evaluate the bioequivalence of three doses of fluconazole capsule 50 mg (Diflucan 50 mg, Pfizer Korea Inc., as a reference drug) and a single dose of fluconazole tablet 150 mg (Plunazol 150 mg, Daewoong Pharm. Co., Korea) according to the guidelines of the Korea Food and Drug Administration (KFDA). The bioequivalence for three capsules of Diflucan 50 mg and a single tablet of Plunazol 150 mg was investigated in twenty-four healthy male volunteers under a randomized 2${\times}$2 crossover trial design. The average age of twenty-four volunteers was 24.78${\pm}$3.27 year-old, average height was 175.56${\pm}$5.45 cm and average weight was 67.24${\pm}$6.86 kg. After three capsules of Diflucan 50 mg or a single tablet of Plunazol 150 mg were orally administered, blood was taken at predetermined time intervals and the plasma concentrations of fluconazole in plasma were determined using LC-MS-MS. The 90% confidence intervals for the main parameters of statistical results after logarithmic transformation were AUCt 0.9272-1.0084 and Cmax 0.8423-0.9544 respectively, which are in the range of log 0.8 to log 1.25 and the statistical results of additional parameters (AUClast, t1/2 and MRT) were also in the 90% confidence interval that is in the range of log 0.8 to log 1.25. Therefore, the results of this study confirm the bioequivalence of three capsules of Diflucan 50 mg to one tablet of Plunazol 150 mg.

• Journal of Pharmaceutical Investigation
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• 제38권4호
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• pp.261-267
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• 2008

The aim of the present study was to evaluate the bioequivalence of two gabapentin preparations. We used Neurontin tablet 800 mg (Pfizer Korea Inc.) as a reference drug for bioequivalence of Gabalep tablet 800 mg (Chong Kun Dang Pharmaceutical Co., Korea), and performed this whole study according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty five healthy male volunteers were administered with each drug in a randomized $2{\times}2$ cross-over study with one week washout interval. After drug administration, blood was taken at predetermined time intervals ($0{\sim}24$ hours) and the concentrations of gabapentin in serum were determined using an high performance liquid chromatography-tandem mass spectrometer (LC-MS/MS) employing electrospray ionization technique and operating in multiple reaction mornitoring (MRM). The analytical method was validated in specificity, accuracy, precision and linearity. The phar-macokinetic parameters such as AUCt and Cmax were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed AUCt and Cmax. $Mean{\pm}SD$. of AUCt and Cmax value for reference drug and test drug were $29.94{\pm}9.23\;({\mu}g/mL{\cdot}hr)$ and $3.12{\pm}1.11\;({\mu}g/mL{\cdot}hr)$, and $31.48{\pm}9.77\;({\mu}g/mL{\cdot}hr)$ and $3.15{\pm}1.03\;({\mu}g/mL)$, respectively. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) for AUCt and Cmax, respectively. These results indicate that Gabalep tablet 800 mg is bioequivalent to Neurontin tablet 800 mg.

• 한국안광학회지
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• 제10권4호
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• pp.293-304
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• 2005

렌즈 세척제인 ReNu$^{TM}$의 안자극테스트를 한국식품의약품안전청의 고시에 따라서 Draize방법(1959)을 사용하여 분석하였다. 부가해서 검사 항목의 잠재성 독성테스트를 위해서 염증세포와 비염증세포의 비율에서 역시 눈 분비물에 대한 세포도말표본사용으로 관찰하였다. 검사에서 각막, 홍채, 망막, 그리고 공막에 대한 조직학적 변화들은 역시 모든 실험동물에서 관찰되었다. 각막과 결막의 약간 자극성은 벼비척그룹에서 점안후 1, 2, 3일에서 관찰되었다. 이러한 지점에서의 안점막자극지수(MIOI)는 각각 4.17, 3.00, 1.33으로 확인되었다. 세척군에서 각막과 결막의 약간의 자극은 각각 0.67과 1.33으로서 MIOI로서 점안후 1일과 2일에서 관찰되었다. 따라서 ReNu$^{TM}$은 비자극성 물질로 생각된다. 왜냐하면 MIOI는 세척군과 비세척군 모두에서 전체 실험기간을 통해서 5.00이하로 관찰되었다. 급성안자극계수(IAOI)는 역시 4.17로서 확인되었다(점안후 일일). 일부의 예외들은 비세척군의 점안후 1일에서 분비물에서 염증세포 비율의 경향이 증가되었다. 그러나 유의성은 없었다. 한편 안분비물의 도말세포관찰에서 의미있는 변화들은 본 연구에서 관찰되었다. 부가해서 각막, 홍채, 공막 위에서 비정상조직 변화는 역시 비처리된 대군군 눈과 비교해서 ReNu$^{TM}$, 점안군에서는 탐지되지 않았다.