• Journal of Pharmaceutical Investigation
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• 제34권4호
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• pp.311-317
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• 2004

A bioequivalence study of $Gomcillin^{TM}$ capsules (DAEWOONG Pharmaceutical Co., Korea) to $Famoxin^{TM}$ capsules (Dong Wha Pharm. Ind. Co., Korea) was conducted according to the guideline of Korea Food and Drug Administration (KFDA). Twenty four healthy male Korean volunteers received each medicine at the amoxicillin dose of 500 mg in a $2{\times}2$ crossover study. There was a one-week wash out period between the doses. Plasma concentrations of amoxicillin were monitored by a high-performance liquid chromatography for over a period of 8 hours after the administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 8 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 $Gomcillin^{TM}/Famoxin^{TM}$ were $log0.91\;{\sim}\;log1.03$ and $;log0.93\;{\sim}\;log1.10$, respectively. These values were within the acceptable bioequivalence intervals of $log0.80\;{\sim}\;log1.25$. Thus, our study demonstrated the bioequivalence of $Gomcillin^{TM}$ and $Famoxin^{TM}$ with respect to the rate and extent of absorption.

• 한국수학교육학회지시리즈E:수학교육논문집
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• 제31권2호
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• pp.139-152
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• 2017

본 논문에서 미적분을 다루는 중등교과서가 미적분 역사를 어떻게 소개하고 있는지를 알아보았다. 문제점을 파악하기 위하여 우리는 기원전 350~기원전 50년에 목성의 위치를 계산하기 위하여 이루어진 바빌로니아인의 사다리꼴을 사용한 구분구적법 그리고 1000년경 이집트에서 이루어진 이븐 알 하이탐(ibn al-Haytham)의 원판을 이용한 구분구적법 등을 고찰하였다. 이를 바탕으로 미적분 역사에 대한 건설적인 서술 방안을 제시하였다. 결론적으로 우리나라 중등수학 교과서는 뉴턴과 라이프니츠가 미적분을 창안한 것으로 설명하고 그 뿌리를 고대 그리스에 둔다. 미적분의 창안은 바빌로니아와 파티마 왕조(Faṭimah Dynasty: 909-1171)(이집트)에 있으며 인도에서 멱급수의 발전이 이루어진 후 미적분이 유럽에서 발전된 것으로 교과서에 아시아 아프리카의 가치가 소개되는 것이 바람직하다.

• Journal of Pharmaceutical Investigation
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• 제35권2호
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• pp.117-122
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• 2005

After establishing improved HPLC analytical method of cefaclor in human plasma samples, a bioavailability study of cefaclor capsules was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). The standard calibration curve using an HPLC with UV detector was constructed in a range of $0.0324{\sim}16\;{\mu}g/ml$. The 6% perchloric acid instead of 6% trichloroacetic acid was used to precipitate plasma protein. The HPLC chromatograms were precisely and accurately resolved when spiked with human plasma spiked with cefaclor and cephalexin (internal standard). Twenty healthy male Korean volunteers received two commercial cefaclor capsules, $Neocef^{\circledR}$ capsule (Jinyang Pharm. Co., Ltd) or $Ceclor^{\circledR}$ capsule (Lilly Korea. Co., Ltd.) at the 250 mg cefaclor in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Plasma concentrations of cefaclor were monitored for 8 hours after oral drug administration. $AUC_t$ the area under the plasma concentration-time curve from time zero to 8 hr (13 points), 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 $Neocef^{\circledR}/Ceclor^{\circledR}$ were $0.9049{\leq}{\delta}{\leq}1.226$, respectively. These values were within the acceptable bioequivalence intervals of 0.80-1.25. Thus, our study demonstrated the bioequivalence of $Neocef^{\circledR}/Ceclor^{\circledR}$ with respect to the extent of absorption.

• Journal of Pharmaceutical Investigation
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• 제35권5호
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• pp.323-328
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• 2005

The purpose of the present study was to evaluate the bioequivalence of two torasemide tablets, Torem tablet (Roche Korea Co., Ltd., Korea, reference drug) and Boryung Torsemide tablet (Boryung Pharmaceutical Co., Ltd., Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). After adding an internal standard (furosemide) to human serum, serum samples were extracted using 5 mL of ethyl acetate. Compounds were analyzed by reverse-phase HPLC method with UV detection. This method showed linear response over the concentration range of 0.05 ug/mL with correlation coefficient of 0.999. The lower limit of quantitation using 0.5 mL of serum was 0.05 ug/mL which was sensitive enough for pharmacokinetic studies. Twenty-eight healthy male Korean volunteers received each medicine at the torasemide dose of 20 mg in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Serum concentrations of torasemide were monitored by an HPLC-UV for over a period of 12 hr after the administration. $AUC_{t}$(the area under the serum concentration-time curve from time zero to 12 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum serum drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the serum 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 Boryung Torsemide/Torem were log 0.97-10g 1.03 and log 0.93log 1.12, respectively. These values were within the acceptable bioequivalence intervals of log 0.80-log 1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating Boryung Torsemide tablet and Torem tablet are bioequivalent.

• Journal of Pharmaceutical Investigation
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• 제40권2호
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• pp.109-115
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• 2010

The purpose of the present study was to evaluate the bioequivalence of two choline alphoscerate soft capsules, Gliatilin soft capsule (Daewoong Pharmaceuticals Co., Ltd.) and Cholicerin soft capsule (Sam Chun Dang Pharm. Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Serum concentrations of choline after oral administration of choline alphoscerate were determined using a validated LC/MS/MS method. This method showed linear response over the concentration range of 0.5-20 ${\mu}g$/mL with correlation coefficient of 0.9999. The lower limit of quantitation using 100 ${\mu}L$ of serum was 0.5 ${\mu}g$/mL which was sensitive enough for pharmacokinetic studies. Thirty six healthy male Korean volunteers received each medicine at the choline alphoscerate dose of 1200 mg in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Blood samples were taken at predetermined time intervals up to 8 hr. $AUC_t$ (the area under the serum concentration-time curve from time 0 to 8 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (the maximum serum drug concentration) and $T_{max}$ (the time to reach $C_{max}$) were compiled from the serum 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 Cholicerin/Gliatilin were log0.9998-log1.1172 and log0.9938-1.0944, respectively. These values were within the acceptable bioequivalence intervals of log0.80-log1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating Cholicerin soft capsule and Gliatilin soft capsule are bioequivalent.

• 한국임상약학회지
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• 제15권1호
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• pp.21-26
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• 2005

A bioequivalence study of CKD $Cefaclor^{(R)}$ capsule (Chong Kun Dang Pharm Co., Ltd) to $Ceclor^{(R)}$ capsule (Lilly Korea 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 cefaclor dose of 250 mg in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. An improved high-performance liquid chromatorgraphy (HPLC) analytical method with UV detection was used to determine plasma cefaclor concentration in human volunteers for 8 hr after oral drug administration. The area under the plasma concentration-time curve from time zero to 8 hr ($AUC_{0-8hr}$) was calculated by the linear trapezoidal rule. the $C_{max}$ (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 $AUC_{0-8hr}\;and\;C_{max}$. 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 $AUC_{0-8hr}$ ratio and the $C_{max}$ ratio for CKD $Cefaclor^{(R)}$ and $Ceclor^{(R)}$ were $0.9400{\leq}{\delta}{\leq}1.0345$ and $0.8858{\leq}{\delta}{\leq}1.1021$, respectively. These values were within the acceptable bioequivalence intervals of 0.80-1.25. Thus, our study demonstrated the of CKD $cefaclor^{(R)}$ capsule was bioequivalent to $Cefaclor^{(R)}$ capsule with respect to its bioavailability.

• Journal of Pharmaceutical Investigation
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• 제28권4호
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• pp.283-288
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• 1998

Lovastatin, one of the potent cholesterol-lowering agents, is an inactive lactone prodrug which is metabolized to its active open acid, lovastatin acid (LVA). Bioequivalence study of two lovastatin preparations, the test drug ($Mevacor^{\circledR}$: Chungwae Pharmaceutical Co., Ltd.) and the reference drug ($Lovaload^{\circledR}$: Chong Kun Dang Pharmaceutical Co., Ltd.), was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Fourteen healthy male volunteers, $23.9{\pm}3.9$ years old and $67.6{\pm}8.0$ kg of body weight in average, were divided randomly into two groups and administered the drug orally at the dose of 160 mg as lovastatin in a $2{\times}2$ crossover study. Plasma concentrations of lovastatin acid were analysed by HPLC method for 12 hr after administration. The extent of bioavailability was obtained from the plasma concentration-time profiles of total lovastatin acid after alkaline hydrolysis of the plasma samples. By alkaline hydrolysis, trace amounts of unmetabolized lovastatin were converted to lovastatin acid. The $AUC_{0-12hr}$ was calculated by the linear trapezoidal rule method. The $C_{max}$ and $T_{max}$ were compiled directly from the plasma drug concentration-time data. Student's t-test indicated no significant differences between the formulations in these parameters. Analysis of variance (ANOVA) revealed that there were no differences in AUC, $C_{max}$, and $T_{max}$ between the formulations. The apparent differences between the formulations were far less than 20% (e.g., 7.07, 5.77 and 1.18% for AUC, $C_{max}$, and $T_{max}$, respectively). Minimum detectable differences(%) between the formulations at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 17.2, 15.1, and 15.9% for AUC, Cmax, and Tmax, respectively). The 90% confidence intervals for these parameters were also within ${\pm}20%$ (e.g.. $-5.20{\sim}19.3$, $-5.00{\sim}16.5$, and $-10.2{\sim}12.5%$ for AUC, $C_{max}$, and $T_{max}$, respectively). These results satisfied the bioequivalence criteria of KFDA guidelines, indicating that the two formulations of lovastatin were bioequivalent.

• Journal of Pharmaceutical Investigation
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• 제37권5호
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• pp.315-321
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• 2007

The purpose of the present study was to evaluate the bioequivalence of two lercanidipine hydrochloride tablets, Zanidip tablet (LG Life Sciences Ltd., Korea, reference drug) and Samchundang Lercanidipine tablet 10 mg (Sam Chun Dang Pharm. Co. Ltd., Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). After adding an internal standard (amlodipine maleate) to human serum, serum samples were extracted using hexan-isoamyl alcohol (100:1, v/v). Compounds were analyzed by liquid chromatography/tandem mass spectrometry. This method showed linear response over the concentration range of 0.05-20 ng/mL with correlation coefficient of 0.9999. The lower limit of quantitation using 0.5 mL of serum was 0.05 ng/mL which was sensitive enough for pharmacokinetic studies. Thirty healthy male Korean volunteers received each medicine at the lercanidipine hydrochloride dose of 20 mg in a $2\;{\times}\;2$ crossover study. There was a one-week washout period between the doses. Serum concentrations of lercanidipine were monitored by an LC/MS/MS fer over a period of 24 hr after the administration. $AUC_t$ (the area under the serum concentration-time curve from time 0 to 24 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (the maximum serum drug concentration) and $T_{max}$ (the time to reach $C_{max}$) were compiled from the serum 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 Samchundang Lercanidipine/Zanidip were log 0.9505-log 1.2258 and log 0.9987-log 1.2013, respectively. These values were within the acceptable bioequivalence intervals of log 0.80-log 1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating Samchundang Lercanidipine tablet 10 mg and Zanidip tablet are bioequivalent.

• Journal of Pharmaceutical Investigation
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• 제29권3호
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• pp.241-245
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• 1999

Bioequivalence study of two cefpodoxime preparations, the test drug ($Banan^{\circledR}$: Hanil Pharmaceutical Co., Ltd.) and the reference drug ($Podox^{\circledR}$: Chong Kun Dang Pharmaceutical Co., Ltd.), was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Sixteen healthy male volunteers, $23.8{\pm}2.13$ years old and $63.34{\pm}4.84kg$ of body weight in average, were divided randomly into two groups and administered the drug orally at the dose of 200 mg as cefpodoxime proxetil in a $2{\times}2$ crossover study. Plasma concentrations of cefpodoxime were analysed by HPLC method for 12 hr after administration. The $AUC_{0-12hr}$ was calculated by the linear trapezoidal rule method. The $C_{max}$, and $T_{max}$ were compiled directly from the plasma drug concentration-time data. Student's t-test indicated no significant differences between the formulations in these parameters. Analysis of variance (ANOVA) revealed that there were no differences in AUC, $C_{max}$, and $T_{max}$ between the formulations. The apparent differences between the formulations were far less than 20% (e.g., 4.31, 1.99 and 4.30% for AUC, $C_{max}$, and $T_{max}$, respectively). Minimum detectable differences (%) between the formulations at ${\alpha}=\;0.05$ and $1-{\beta}=\;0.8$ were less than 20% (e.g., 13.89, 13.88, and 16.97% for AUC, $C_{max}$, and $T_{max}$, respectively). The 90% confidence intervals for these parameters were also within ${\times}20%$ (e.g., $-5,58{\sim}14.20$, $-7.89{\sim}11.88$, and $-7.78{\sim}16.38%$ for AUC, $C_{max}$, and $T_{max}$, respectively). These results satisfied the bioequivalence criteria of KFDA guidelines, indicating that the two formulations of cefpodoxime were bioequivalent.

• Journal of Pharmaceutical Investigation
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• 제38권2호
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• pp.135-142
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• 2008

The present study describes the evaluation of the bioequivalence of two atorvastatin tablets, Lipitor $Tablet^{(R)}$ (Pfizer, reference drug) and Atorva $Tablet^{(R)}$ (Yuhan, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Forty-nine healthy male Korean volunteers received each medicine at the atorvastatin dose of 40 mg in a $2{\times}2$ crossover study with a two weeks washout interval. After drug administration, serial blood samples were collected at a specific time interval from 0-48 hours. The plasma atorvastatin concentrations were monitored by an high performance liquid chromatography -tandem mass spectrometer (LC-MS/MS) employing electrospray ionization technique and operating in multiple reaction monitoring (MRM) and positive ion mode. The total chromatographic run time was 4.5 min and calibration curves were linear over the concentration range of 0.1-100 ng/mL for atorvastatin. The method was validated for selectivity, sensitivity, linearity, accuracy and precision. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 48hr) was calculated by the linear log trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were complied trom 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 Atorva $Tablet^{(R)}$ / Lipitor $Tablet^{(R)}$ were ${\log}\;0.9413{\sim}{\log}\;1.0179$ and ${\log}\;0.831{\sim}{\log}\;1.0569$, respectively. These values were within the acceptable bioequivalence intervals of ${\log}\;0.8{\sim}{\log}\;1.25$. Based on these statistical considerations, it was concluded that the test drug, Atorva $Tablet^{(R)}$ was bioequivalent to the reference drug, Lipitor $Tablet^{(R)}$.