• Journal of Pharmaceutical Investigation
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• v.31 no.4
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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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• v.33 no.3
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• pp.215-221
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• 2003

A bioequivalence study of $Ambrect^{TM}$ tablets (Dong Wha Pharm. Ind. Co., Ltd.) to $Mucopect^{TM}$ tablets (Boehringer Ingelheim Korea, Ltd.) was conducted according to the guideline of Korea Food and Drug Administration (KFDA). Twenty four healthy male Korea volunteers received each medicine at the ambroxol hydrochloride dose of 30 mg in a $2{\times}2$ crossover study. There was a one-week wash out period between the doses. Plasma concentrations of ambroxol were monitored by a high-performance liquid chromatography for over a period of 24 hours after the administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 24 hr) was calulated 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 $Ambrect^{TM}/Mucopect^{TM}$ were 0.89-1.01 and 0.89-1.02, respectively. These values were within the acceptable bioequivalence intervals of 0.80-1.25. Thus, our study demonstrated the bioequivalence of $Ambrect^{TM}\;and\;Mucopect^{TM}$ with respect to the rate and extent of absorption.

• Journal of Pharmaceutical Investigation
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• v.36 no.3
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• pp.193-199
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• 2006

A bioequivalence study of $Sudo^{TM}$ Ranitidine HCI tablet (Sudo Pharma. Ind. Co., Ltd.) to $Curan^{TM}$ tablet (Il Dong 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 ranitidine hydrochloride dose of 150 mg in a 2x2 crossover study. There was a one week wash-out period between the doses. Plasma concentrations of ranitidine were monitored by a high-turbulent liquid chromatography (HTLC) for over a period of 12 hours after drug administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 12 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 far 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 $Sudo^{TM}$ Ranitidine $HCl/Curan^{TM}$ were 0.92-1.00 and 0.90-1.03, respectively. These values were within the acceptable bioequivalence intervals of 0.80-1.25. Thus, our study demonstrated the bioequivalence of $Sudo^{TM}$ Ranitidine HCI and $Curan^{TM}$ with respect to the rate and extent of absorption.

• Journal of Pharmaceutical Investigation
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• v.34 no.5
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• pp.413-418
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• 2004

A bioequivalence of $Melax^{TM}$ capsules (Chong Kun Dang Pharm., Korea) and $Mobic^{TM}$ capsules (Boehringer Ingelheim Korea) was evaluated according to the guideline of Korea Food and Drug Administration (KFDA). Single 15 mg dose of meloxicam of each medicine was administered orally to 24 healthy male volunteers. This study was performed in a $2\;{\times}\;2$ crossover design. Concentrations of meloxicam in human plasma were monitored by a high-performance liquid chromatography. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 72 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 performed using logarithmically transformed $AUC_t$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for $Melax^{TM}/Mobic^{TM}$ were 0.95 - 1.04 and 0.98 - 1.14, respectively. This study demonstrated a bioequivalence of $Melax^{TM}$ and $Mobic^{TM}$ with respect to the rate and extent of absorption.

• Journal of Pharmaceutical Investigation
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• v.36 no.2
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• pp.137-142
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• 2006

A bioequivalence of Daewoong $Alendronate^{TM}$ (Daewoong Pharmaceutical Co., Ltd., Korea) and $Fosamax^{TM}$ tablets (MSD Korea) was evaluated according to the guideline of Korea Food and Drug Administration (KFDA). A single 70 mg dose of sodium alendronate of each medicine was administered orally to 56 healthy male volunteers. This study was performed in a $2\;{\time}\;2$ crossover design. Concentrations of alendronate in the urine were monitored by a high-performance liquid chromatography (HPLC). $A_{et}$ (cumulative urinary excreted amount from time 0 to last sampling interval) was calculated by the accumulation of the urinary excreted alendronate. $U_{max}$ (maximum urinary excretion rate) and $T_{max}$ (time to reach $U_{max}$) were compiled from the urinary excretion rate - time data. Analysis of variance was performed using logarithmically transformed $A_{et}$ and $U_{max}$. No significant sequence effect was found for all of the bioavailability parameters. The 90% confidence intervals of the $A_{et}$ and $U_{max}$ for Daewoong $Alendronate^{TM}/Fosamax^{TM}$ were 0.89-1.12 and 0.82-1.02, respectively. This study demonstrated the bioequivalence of Daewoong $Alendronate^{TM}$ and $Fosamax^{TM}$ with respect to the rate and extent of absorption.

• Journal of Pharmaceutical Investigation
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• v.39 no.2
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• pp.133-139
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• 2009

The purpose of the present study was to evaluate the bioequivalence of two pioglitazone HCl tablets, $Actos^{TM}$, tablets (Lilly Korea. Ltd., Korea) as a reference drug and $Piros^{TM}$, tablets (Reyon Pharm. Co., Ltd., Korea) as test drug, according to the guideline of Korea Food and Drug Administration (KFDA). Twenty-four healthy male Korean volunteers received one tablet containing pioglitazone HCl 15 mg in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Plasma concentrations of pioglitazone were monitored for over a period of 36 hr after administration by using a high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The area under the plasma concentration-time curve from time zero to 36 hr ($AUC_{0-36hr}$), maximum plasma drug concentration ($C_{max}$) and time to reach $C_{max}$ ($T_{max}$) were complied from the plasma concentration-time data. Analysis of variance (ANOVA) test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_{0-36hr}$ and $C_{max}$. The 90% confidence intervals of the $AUC_{0-36hr}$ ratio and the $C_{max}$ ratio for $Piros^{TM}$/$Actos^{TM}$. were log 0.8753-log 1.1286 and log 0.8669-log 1.1734, respectively. These values were within the acceptable bioequivalence intervals of log 0.80-log 1.25, recommended by KFDA. In all of these results, we concluded that the $Piros^{TM}$. tablet was bioequivalent to the $Actos^{TM}$. tablet, based on the rate and extent of absorption.

• Journal of Pharmaceutical Investigation
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• v.34 no.3
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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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• v.34 no.4
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• pp.319-325
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• 2004

A bioequivalence of $Etodol^{TM}$ tablets (Yuhan corporation) and $Kuhnillodine^{TM}$ tablets (Kuhnil Pharm. Co., Ltd.) was evaluated according to the guideline of Korea Food and Drug Administration (KFDA). Single 200 mg dose of etodolac of each medicine was administered orally to 24 healthy male volunteers. This study was performed in a $2{\times}2$ crossover design. Concentrations of etodolac in human plasma were monitored by a high-performance liquid chromatography. $AUC_t$ (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 performed using logarithmically transformed $AUC_t$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for $Etodol^{TM}/Kuhnillodine^{TM}$ were 1.01-1.10 and 0.87-1.06, respectively. This study demonstrated a bioequivalence of $Etodol^{TM}$ and $Kuhnillodine^{TM}$ with respect to the rate and extent of absorption.

• Korean Journal of Clinical Pharmacy
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• v.7 no.2
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• pp.73-80
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• 1997

The bioequivalence of two loxoprofen tablets between the $Loxonin^{TM}$ (Dong Hwa Pharmaceutical Co., Ltd.) and the $Lokpen^{TM}$ (Dong Il Pharmaceutical Co., Ltd.) was evaluated. 12 normal male volunteers (age $21\sim27$ years old) were divided into two groups and a randomized cross-over study was employed. After one tablet containing 60 mg of loxoprofen sodium anhydrous was orally administered, blood was taken at predetermined time intervals and the concentration of loxoprofen in serum was determined with an HPLC method using UV/VIS detector. The pharmacokinetic parameters ($C_{max},\;T_{max}$, and $AUC_t$) were calculated and ANOVA was utilized for the statistical analysis of parameters. The results showed that the differences in $C_{max},\;T_{max}$, and $AUC_t$ between two tablets were $1.13\%,\;0\%,\;and\;0.69\%$, respectively The powers (1-${\beta}$) for $C_{max},\;T_{max}$, and $AUC_t$ were $84.88\%,\;88.61\%,\;and\;84.81\%$, respectively Detectable differences ($\delta$) and confidence intervals were all less than $20\%$. All of these parameters met the criteria of KFDA for bioequivalence, indicating that $Lokpen^{TM}$ tablet is bioequivalent to $Loxonin^{TM}$ tablet.

• Journal of Pharmaceutical Investigation
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• v.29 no.3
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• pp.235-240
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• 1999

Bioequivalence of two clarithromycin tablets, the $Klaricid^{TM}$ (Ciba-Geigy Korea Ltd., Seoul, Korea) and the LG clarithromycin (LG Chemical Co., Ltd., Seoul, Korea), was evaluated according to the Korean Guidelines for Bioequivalence Test (KGBT 1998). Sixteen normal male volunteers $(20{\sim}26\;years\;old)$ were randomly divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 250 mg of clarithromycin was orally administered, blood sample was taken at predetennined time intervals, and the concentrations of clarithromycin in serum were detennined using HPLC method with electrochemical detector. The pharmacokinetic parameters $(AUC_t,\;C_{max}\;and\; T_{max})$ were calculated and 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 4.06%,2.67% and -9.70%, respectively. The powers $(1-{\beta})$ for $AUC_t$, $C_{max}$ and $T_{max}$ were 83.53%, 92.34% and 96.64%, respectively. Detectable differences $({\Delta})$ and 90 % confidence intervals $(a=0.05) $were all less than ${\pm}20%$. All the parameters above met the criteria of KGBT 1998, indicating that LG clarithromycin tablet is bioequivalent to $Klaricid^{TM}$ tablet.