• Korean Journal of Clinical Pharmacy
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• v.11 no.1
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• pp.7-12
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• 2001

Cilostazol has both antithrombotic and cerebral vasodilating effects, and one of the mechanism is the selective inhibition of platalet cyclic AMP phosphodiesterase. Bioequivalence of two cilostazol tablets, the $Pletaal^{TM}$ (Korea Otsuka Pharmaceutical Co.) and the LG $Cilostazol^{TM}$ (LG Chemical Co.), was evaluated according to the guidelines of Korea Food and Drug Administration (KFDA). Sixteen normal male volunteers ($20\sim29$ years old) were randomly divided into two groups and a randomized $2\times2$ cross-over study was employed. After oral administration of $Pletaal^{TM}$ or LG $Cilostazol^{TM}$ tablet (100 mg cilostazol), blood samples were taken at predetermined time intervals and the serum cilostazol concentrations were determined using an HPLC method with UV/VIS detector. The pharmacokinetic parameters $(AUC_t,\;C_{max}\;and\;T_{max})$ were calculated and ANOVA was utilized for the statistical analysis. The results showed that the differences in AUCt, C_{max} and Tmax between two tablets based on the $Pletaal^{TM}$ tablet were $-5.39\%,\;2.32\%\;and\;4.26\%$, respectively. The powers (1-${\beta}$) for $AUC_t,\;C_{max}\;and\;T_{max}\;were\;83.81\%,\;96.02\%\;and\;91.04%$, respectively. Minimum detectable differences ($\Delta$) and $90\%$ confidence intervals were all less than $\pm20\%$. All these parameters met the criteria of KFDA for bioequivalence, indicating that LG $Cilostazol^{TM}$ tablet is bioequivalent to $Pletaal^{TM}$ tablet.

• Journal of Pharmaceutical Investigation
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• v.33 no.3
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• pp.229-235
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• 2003

The purpose of the present study was to evaluate the bioequivalence of two enalapril maleate tablets, $Renitec^{TM}$ (MSD Korea Ltd.) and $Enalace^{TM}$ (Welfide Korea Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four normal male volunteers, $22.33{\pm}2.55$ year in age and $66.54{\pm}8.30$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After two tablets containing 10 mg of enalapril maleate per tablet were orally administered, blood was taken at predetermined time intervals and concentrations of enalapril in plasma were determined using LC-MS-MS. 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 $AUC_t,\;and\;C_{max}$ untransformed $T_{max}$. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals for the log transformed data were acceptance range of log0.8 to log1.25$(e.g.,\;log1.02{\sim}log1.14\;and\;log1.03{\sim}log1.19\;for\;AUC_t\;and\;C_{max},\;respectively)$. The major parameters, $AUC_t,\;and\;C_{max}$, met the criteria of KDFA for bioequivalence indicating that $Enalace^{TM}$ tablet is bioequivalent to $Renitec^{TM}$ tablet.

• Journal of Pharmaceutical Investigation
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• v.29 no.1
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• pp.61-66
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• 1999

Bioequivalence of two terazosin tablets, the $Hytrine^{TM}$ (Il-Yang Pharmaceutical Co., Ltd.) and the $Hytrine^{TM}$ (Daewon Pharmaceutical Co., Ltd.), was evaluated according to the guideline of KFDA. Sixteen normal male volunteers $(21{\sim}30\;years\;old)$ were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 2 mg of terazosin was orally administered, blood was taken at predetermined time intervals and the concentration of terazosin in serum was determined with a HPLC method using spectrofluorometric detector. The pharmacokinetic parameters $(AUC_t,\;C_{max}\;and\;T_{max})$ were calculated and ANOVA 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 were 6.02%,3.44% and -3.67%, respectively. The powers $(1-{\beta})$ for $AUC_t$, $C_{max}$ and $T_{max}$ were 98.05%, 98.34% and 29.81 %, respectively. Detectable differences $({\Delta})$ and confidence intervals were all less than ${\pm}20%$ except $T_{max}$. $AUC_t$ and $C_{max}$ met the criteria of KFDA for bioequivalence, indicating that $Terasin^{TM}$ tablet is bioequivalent to $Hytrine^{TM}$ tablet.

• Journal of Pharmaceutical Investigation
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• v.29 no.1
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• pp.67-72
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• 1999

A bioequivalence study of the $Kerola^{\circledR}$ intramuscular injections (Dongkwang Pharmaceutical Co., Korea) to the $Tarasyn^{\circledR}$ intramuscular injections (Roche Co., Korea), formulations of ketorolac tromethamine (KTR), was conducted. Sixteen healthy Korean male subjects were received each formulation at the dose of 30 mg as KTR in a $2{\times}2$ crossover study. There was an one-week washout period between the doses. Plasma concentrations of KTR were monitored by a HPLC method. AUC was calculated by the linear trapezoidal method. $C_{max}$ and $T_{max}$ 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 differences between the formulations in these parameters were all far less than 20% (i.e., 3.65, 2.59 and 4.35% for AUC, $C_{max}$ and $T_{max}$ respectively). Minimum detectable differences (%) at ${\alpha}=0.1$ and $1-{\beta}=0.8$ were 12.87, 13.44, 20.62%, for AUC, $C_{max}$ and $T_{max}$, respectively. The 90% confidence intervals for these parameters were also within 20%. These results satisfy the bioequivalence criteria of the Korea Food and Drug Administration (KFDA) guidelines (No. 1998-86). Therefore, these results indicate that the two formulations of KTR are bioequivalent.

• Journal of Pharmaceutical Investigation
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• v.35 no.1
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• pp.45-50
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• 2005

The purpose of the present study was designed to evaluate the bioequivalence of two ofloxacin tablets, Tarivid (Jeil Pharm. Co., Ltd.) and Favid (ILHWA Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four normal male volunteers, $23.67{\pm}3.12$ year in age and $68.50{\pm}7.23$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After four tablets containing 100 mg of ofloxacin were orally administered, blood was taken at predetermined time intervals and concentrations of ofloxacin in plasma were determined using HPLC. 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 $AUC_t$ and $C_{max}$ and untransformed $T_{max}$. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals for the log transformed data were acceptance range of log 0.8 to log 1.25 (e.g., $log0.94{\sim}log1.04\;and\;log0.90{\sim}log1.07\;for\;AUC_t\;and\;C_{max}$, respectively). The major parameters, $AUC_t$, and $C_{max}$, met the criteria of KDFA for bioequivalence indicating that Favid tablet is bioequivalent to Tarivid tablet.

• Journal of Pharmaceutical Investigation
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• v.35 no.3
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• pp.187-192
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• 2005

The purpose of the present study was designed to evaluate the bioequivalence of two benidipine hydrochloride tablets, Codipine (Youngjin Pharm. Co., Ltd.) and Benipine (Myungmoon Pharm. Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four normal male volunteers, $23.00{\pm}1.82$ year in age and $70.08{\pm}9.59$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After two tablets containing 4 mg of benidipine hydrochloride were orally administered, blood was taken at predetermined time intervals and concentrations of benidipine in plasma were determined using LC-MS/MS. 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 $AUC_t$, and $C_{max}$. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals for the log transformed data were acceptance range of log0.8 to log1.25 $(e.g., \;log1.04{\sim}log1.24\;and\;log0.91{\sim}log1.09$ for $AUC_t$, and $C_{max}$ respectively). The major parameters, $AUC_t$ and $C_{max}$, met the criteria of KDFA for bioequivalence indicating that Benipine tablet is bioequivalent to Codipine tablet.

• Journal of Pharmaceutical Investigation
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• v.28 no.3
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• pp.193-198
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• 1998

Bioequivalence of two cilostazol tablets, the $Pletaal^{TM}$ (Korea Otsuka Pharmaceutical Co., Ltd.) and the $Losazol^{TM}$ (Kyoung Dong Pharmaceutical Co., Ltd.), was evaluated according to the guideline of KFDA. Fourteen normal male volunteers (age $20{\sim}28$ years old) were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After two tablets containing 50 mg of cilostazol were orally administered, blood was taken at predetermined time intervals and the concentration of cilostazol in plasma was determined with an HPLC method using UV 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 3.14%, 10.0% and 7.35%, respectively. The powers $(1-{\beta})$ for $C_{max},\;T_{max}\;and\;AUC_t$ were 89.67%, 80.97% and 83.87%, respectively. Detectable differences $({\Delta})$ and confidence intervals were all less than 20% except $T-{max}$, but confidence interval of $T_{max}$ was also less than 20% at the significance $level({\alpha})$ of 0.1. All of these parameters met the criteria of KFDA for bioequivalence, indicating that $Losazol^{TM}$ tablet is bioequivalent to $Pletaal^{TM} tablet$.

• Journal of Pharmaceutical Investigation
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• v.35 no.5
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• pp.355-360
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• 2005

The purpose of the present study was to evaluate the bioequivalence of two cetirizine HCl tablets, Zyrtec tablet (UCB Pharm. Co., Ltd. Korea, reference product) and Zyrix tablet (Kukje Pharm. Co., Ltd., Korea, test product), according to the guidelines of Korea Food and Drug Administration (KFDA). After adding an internal standard (diazepam), plasma samples were extracted using 1 mL of dichloromethane. Compounds extracted were analyzed by reverse-phase HPLC with ultra-violet detector. This method for determination cetirizine is proved accurate and reproducible with a limit of quantitation of 10 ng/mL in male plasma. Twenty-four healthy male Korean volunteers received each medicine at the cetirizine HCl dose of 10 mg in a $2{\times}2$ crossover study. There was a one-week wash out period between the doses. Plasma concentrations of cetirizine were monitored for over a period of 24 hr after the administration. AUC (the area under the plasma concentration-time curve) was calculated by the linear trapezoidal rule. $C_{max}$ (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 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 for the log transformed data were acceptable range of log 0.8 to log 1.25 $(e.g.,\;log\;0.93-log\;1.08\;for\;AUC_{0-t},\;log\;0.91-log\;1.08\;for\;AUC_{0-{\infty}}\;and\;log\;1.01-log\;1.11\;for\;C_{max})$. The major parameters, AUC and $C_{max}$ met the criteria of KFDA for bioequivalence indicating that Zyrix tablet is bioequivalent to Zyrtec tablet.

• Journal of Pharmaceutical Investigation
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• v.29 no.2
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• pp.151-156
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• 1999

Bioequivalence of two fluoxetine capsules, the $Prozac^{\circledR}$ (Daewoong Lilly Pharmaceutical Co., Ltd.) and the $Lucetin^{\circledR}$ (Kyungdong Pharmaceutical Co., Ltd.), was evaluated according to the guideline of KFDA. Twenty normal male volunteers $(21{\sim}30\;years\;old)$ were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After three capsules containing 20 mg of fluoxetine per capsule were orally administered, blood was taken at predetermined time intervals, and the concentrations of fluoxetine in serum were determined using HPLC method with UV detector. The pharmacokinetic parameters ($AUC_t$, $C_{max}$ and $T_{max}$) were calculated and ANOVA test was utilized for the statistical analysis of parameters. The results showed that the differences in $AUC_t$, $C_{max}$ and $T_{max}$ between two capsules based on $Lucetin^{\circledR}$ capsules were -8.01 %, -7.02% and 1.49%, respectively. The powers $(1-{\beta})$ for $AUC_t$, $C_{max}$ and $T_{max}$ were 84.72%, 96.68% and 83.06%, respectively. Detectable differences $({\Delta})$ and confidence intervals were all less than ${\pm}20%$. All the parameters above met the criteria of KFDA for bioequivalence, indicating that $Lucetin^{\circledR}$ capsule is bioequivalent to $Prozac^{\circledR}$ capsule.

• Journal of Pharmaceutical Investigation
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• v.37 no.4
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• pp.249-254
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• 2007

The purpose of the present study was to evaluate the bioequivalence of two baclofen tablets, $Baclan^{TM}$ tablet (Yooyoung Pharm. Co., Ltd., Seoul, Korea, reference drug) and Taepyungyang Baclofen tablet (Pacificpharma Corporation, Seoul, Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four healthy male Korean volunteers received three tablets containing baclofen 10 mg in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Plasma concentrations of baclofen were monitored for over a period of 24 hr after the administration by using an LC-MS/MS. $AUC_t,\;C_{max}\;and\;T_{max}$ were compiled from the plasma concentration-time data. Analysis of variance (ANOVA) test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t\;and\;C_{max}$. The 90% confidence intervals of the $AUC_t$ and the $C_{max}$ for Taepyungyang $Baclofen/Baclan^{TM}$ were $log0.92{\sim}log1.06\;and\;log1.03{\sim}log1.22$, respectively. These values were within the acceptable bioequivalence intervals of $log0.80{\sim}log1.25$. It was concluded that Taepyungyang Baclofen tablet was bioequivalent to $Baclan^{TM}$ tablet, in terms of both rate and extent of absorption.