• 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.28 no.4
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• pp.289-294
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• 1998

Bioequivalence of two aceclofenac tablets, the $Airtal^{TM}$ (Daewoong Pharmaceutical Co., Ltd.) and the $Senital^{TM}$ (Hana Pharmaceutical Co., Ltd.), was evaluated according to the guideline of KFDA. Fourteen normal male volunteers (age $20{\sim}29$ years old) were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 100 mg of aceclofenac was orally administered, blood was taken at predetermined time intervals and the concentration of aceclofenac 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 3.69%, 2.44% and 0.51%, respectively. The powers $(1-{\beta})$ for $C_{max}$, $T_{max}$ and $AUC_t$ were 87.85%, 98.70% and more than 99%, respectively. Detectable differences $({\Delta})$ and confidence intervals were all less than ${\pm}20%$. All of these parameters met the criteria of KFDA for bioequivalence, indicating that $Senital^{TM}$ tablet is bioequivalent to $Airtal^{TM}$ tablet.

• 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.37 no.1
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• pp.57-62
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• 2007

The purpose of the present study was to evaluate the bioequivalence of two donepezil tablets, $Aricept^{TM}$ tablet (Dae Woong Pharm. Co., Ltd., Korea, reference drug) and $Donpezil^{TM}$ tablet (Dong Wha Pharm. Ind. Co., Ltd., Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four healthy male Korean volunteers received one tablet containing donepezil hydorchloride 10 mg in a $2{\times}2$ crossover study. There was a three-week washout period between the doses. Plasma concentrations of donepezil were monitored by an LC-MS/MS far over a period of 240 hr after the administration. $AUC_t$, (the area under the plasma concentration-time curve from time zero to 240 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 effects were found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ and $C_{max}$ were log 0.95${\sim}$log 1.03 and log 0.94${\sim}$log 1.08, respectively. These values were within the acceptable bioequivalence intervals of log 0.80${\sim}$log 1.25. Taken together, our study demonstrated the bioequivalence of $Aricept^{TM}$ and $Donpezil^{TM}$ with respect to the rate and extent of absorption.

• 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.31 no.2
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• pp.131-136
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• 2001

Tofisopam is a new type of tranquilizer valuable for the relief of anxiety and tension in a wide range of emotional disorders. Tofisopam has the therapeutic characteristics of a minor tranquilzer and a mild stimulatory effect. The purpose of the present study was to evaluate the bioequivalence of two tofisopam tablets, $Grandaxin^{TM}$ (Hwan In Pharmaceutical Co., Ltd.) and $Tofim^{TM}$ (Kyung Dong Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers, $23.11\;{\pm}\;2.83$ years in age and $65.43\;{\pm}\;7.64\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 50 mg of tofisopam was orally administered, blood was taken at predetermined time intervals and the concentrations of tofisopam in serum were determined using HPLC method with UV detector. 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 $Grandaxin^{TM}$ were -5.59%, 2.22% and -13.18%, respectively. Minimum detectable differences $({\Delta})$ at ${\alpha}=0.10$ and $1-{\beta}=0.8$ were less than 20% (e.g., 14.95% and 19.34% for $AUC_t\;and\;C_{max}$, respectively). The powers $(1-{\beta})$ at ${\alpha}=0.10$, ${\Delta}=0.2$ for $AUC_t$ and $C_{max}$ were 95.21% and 81.93%, respectively. The 90% confidence intervals were within {\pm}20%$ (e.g., $-15.64{\sim}4.45$ and $-10.77{\sim}15.21$ for $AUC_t\;and\;C_{max}$, respectively). Two parameters met the criteria of KFDA for bioequivalence, indicating that $Tofim^{TM}$ tablet is bioequivalent to $Grandaxin^{TM}$ tablet.

• Journal of Pharmaceutical Investigation
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• v.31 no.2
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• pp.125-130
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• 2001

Bucillamine is a novel cysteine derivative with two free intramolecular sulfhydryl groups, and has a preventive and therapeutic effect on adjuvant arthritis, suggesting its antirheumatic action. With respect to the effect on the immune system, bucillamine-exerted such immunoregulating actions are to nomalize an excessive reduction or acceleration in immune reaction. It is useful not only in patients with early stage of rheumatoid arthritis (RA) but also in those with active RA retained for more than 10 years. The purpose of the present study was to evaluate the bioequivalence of two bucillamine tablets, $Rimatil^{TM}$ (Chong Kun Dang Pharmaceutical Co., Ltd.) and $Bucilin^{TM}$ (Kuhn Il Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers, $23.67{\pm}2.09$ years in age and $65.03{\pm}6.73\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After three tablets containing 100 mg of bucillamine per tablet were orally administered, blood was taken at predetermined time intervals and the concentrations of bucillamine in serum were determined using GC/MS with mass selective detector. 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 were -0.29%, -3.20% and 8.22%, respectively, when calculated against the $Rimatil^{TM}$ tablet. The powers $(1-{\beta})$ for $AUC_t\;and\;C_{max}$ were 84.31 % and 91.16%, respectively. Minimum detectable differences $({\Delta})$ at ${\alpha}=0.10$ and $1-{\beta}=0.8$ were less than 20% (e.g., 18.58% and 16.51% for $AUC_t\;and\;C_{max}$, respectively). The 90% confidence intervals were within ${\pm}20%$ (e.g.,$-12.77{\sim}12.20$ for $AUC_t$ and $-14.30{\sim}7.90$ for $C_{max}$). Two parameters met the criteria of KFDA for bioequivalence, indicating that $Bucilin^{TM}$ tablet is bioequivalent to $Rimatil^{TM}$ tablet.

• Journal of Pharmaceutical Investigation
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• v.35 no.3
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• pp.193-199
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• 2005

Gabapentin is an antiepileptic drug that is structurally similar to ${\gamma}-aminobutyric$ acid (GABA), but does not interact with the GABA receptor. It does not bind significantly to plasma proteins, and is excreted to unchanged form in the urine. The purpose of the present study was to evaluate the bioequivalence of two gabapentin capsules, $Neurontin^{TM}$ capsule 300 mg (Pfizer Pharm. Co., Ltd.) and Kuhnil $Gabapentin^{TM}$ capsule 300 mg (Kuhnil Pharm. Co., Ltd), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of gabapentin from the two gabapentin 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 six healthy male subjects, $22.46{\pm}1.86$ years in age and $67.64{\pm}7.24$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single capsule containing 300 mg as gabapentin was orally administered, blood samples were taken at predetermined time intervals and the concentrations of gabapentin in serum were determined using HPLC with fluorescence detector. 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, $Neurontin^{TM}$ capsule 300 mg, were -2.03, -0.43 and 4.29% 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 $(e.g.,\;log\;0.89{\sim}log\;1.09\;and\;log\;0.91{\sim}log\;1.09$ for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Kuhnil $Gabapentin^{TM}$ capsule 300 mg was bioequivalent to $Neurontin^{TM}$ capsule 300 mg.

• Journal of Pharmaceutical Investigation
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• v.31 no.1
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• pp.49-55
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• 2001

Acetyl-L-carnitine (ALC), an endogenous component of the L-carnitine family, is naturally occurring molecule synthesized from L-carnitine (LC) by carnitine acetyl transferase. ALC has been shown to improve the cognitive performance of patients suffering from dementia of the Alzheimer's type and proposed for treating Alzheimer's disease in pharmacological doses. The purpose of the present study was to evaluate the bioequivalence of two ALC tablets, $Nicetile^{TM}$ (Dong-A pharmaceutical Co., Ltd.) and $Neurocetil^{TM}$ (Kyung-Dong Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration. Twenty six normal male volunteers, $22.80{\pm}2.76$ year in age and $63.07{\pm}7.98\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 500 mg of ALC was orally administered, blood was taken at predetermined time intervals and the concentrations of ALC in serum were determined using HPLC with fluorescence detector. Because of the presence of endogenous ALC, the calibration was performed using dialyzed serum. Pharmacokinetic parameters such as $AUC_t$, $C_{max}\;and\;T_{max}$ 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 2.72%, -0.65% and -8.42%, respectively, when calculated against the $Nicetile^{TM}$ tablet. The powers $(1-{\beta})$ for $AUC_t\;and\;C_{max}$ were 94.87% and 87.17%, respectively. Minimum detectable differences $({\Delta})$ at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 15.58% and 19.16% $AUC_t\;C_{max}$, respectively). The 90% confidence intervals were within ${\pm}20%$ (e.g., $-11.84{\sim}6.41$ and $-10.57{\sim}11.88$for $AUC_t\;and\;C_{max}$, respectively). Two parameters met the criteria of KFDA for bioequivalence, indicating that $Neurocetil^{TM}$ tablet is bioequivalent to $Nicetile^{TM}$ tablet.

• Journal of Pharmaceutical Investigation
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• v.31 no.1
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• pp.57-62
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• 2001

Azelastine, a phthalazinone derivative, is an antiallergic agent which demonstrates histamine $H_1-receptor$ antagonist activity and also inhibits histamine release from mast cells following antigen and non-antigen stimuli. Thus, azelastine may be useful in the management of both asthma and allergic disorders. The purpose of the present study was to evaluate the bioequivalence of two azelastine hydrochloride tablets, $Azeptin^{TM}$ (Bu Kwang Pharmaceutical Co., Ltd.) and $Azela^{TM}$ (Kyung Dong Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers, $22.44{\pm}2.01$ years in age and $61.99{\pm}6.18\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After two tablets containing 1 mg of azelastine hydrochloride per tablet were orally administered, blood was taken at predetermined time intervals and the concentrations of azelastine in serum were determined using HPLC with fluorescence detector. 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 were -6.45%, -2.60% and -7.14%, respectively, when calculated against the $Azeptin^{TM}$ tablet. The powers $(1-{\beta})$ for $AUC_t\;and\;C_{max}$ were 96.65% and 88.47%, respectively. Minimum detectable differences $({\Delta})$ at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 14.40% and 17.65% for $AUC_t\;and\;C_{max}$, respectively). The 90% confidence intervals were within ${\pm}20%$ (e.g., $-14.87{\sim}1.97$ and $-12.92{\sim}7.72$ for $AUC_t\;and\;C_{max}$, respectively). Two parameters met the criteria of KFDA for bioequivalence, indicating that $Azela^{TM]$ tablet is bioequivalent to $Azeptin^{TM}$ tablet.