• 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.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.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.

• 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.

• Korean Journal of Clinical Pharmacy
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• v.11 no.2
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• pp.49-56
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• 2001

Acetyl-L-carnitine (ALC), an endogenous component of the L-carnitine family, is a naturally existing 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 bioefuivalence of two ALC tablets, $Nicetile^{TM} (Dong-A Pharmaceutical Co.) and $L-Cartin^{TM}$ (Kuhn Il Pharmaceutical Co.), according to the guidelines of Korea Food and Drug Administration (KFDA). The ALC release from the two ALC tablets in vitro was tested using KP VII Apparatus II method in various dissolution media (pH 1.2, 6.0 and 6.8). Twenty six normal male volunteers, $24.46\pm3.67$ years in age and $64.45\pm5.54$ kg in body weight, were divided into two groups and a randomized $2\times2$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. The dissolution profiles of the two ALC tablets were similar in all the dissolution media. The 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 $0.35\%,\;0.93\%\;and\;2.34\%$ respectively, when calculated against the $Nicetile^{TM} tablet. The powers $(1-\beta)\;for\;AUC_t$ , and Cmax were $98.72\%\;and\;85.48\%$, respectively. Minimum detectable differences $(\Delta)\;at\;\alpha=0.05\;and\;1-\beta=0.8$ were less than $20\%,\;(e.g.,\;13.21\%\;and\;18.42\%\;for\;AUC_t,\;and\;C_{max}$ respectively). The $90\%$ confidence intervals were within $\pm20\%\;(e.g.,\;-7.38\sim8.09\;and\;-9.86\sim11.72\;for\;AUC_t,\;and\;C_{max}$, respectively). These two parameters met the criteria of KFDA for bioequivalence, indicating that $L-Cartin^{TM}$ tablet is bioequivalent to $Nicetile^{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.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.

• Journal of Pharmaceutical Investigation
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• v.30 no.1
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• pp.61-65
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• 2000

Doxazosin, a postsynaptic selective ${\alpha}1-adrenoceptor$ antagonist, is a potent antihypertensive agent which reduces peripheral resistance and blood pressure by vasodilatation of peripheral vessels. It is also used in the treatment of urinary obstruction by benign prostatic hypertrophy. The purpose of the present study was to evaluate the bioequivalence of two doxazosin tablets, $Cardura^{TM}$ (Pfizer Korea Ltd.) and $Cardil^{TM};$ (Kyungdong Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Sixteen normal male volunteers, $24.19{\pm}2.48$ years in age and $62.41{\pm}6.66$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 2 mg of doxazosin was orally administered, blood was taken at predetermined time intervals and the concentrations of doxazosin in serum were determined with an HPLC method using spectrofluorometric 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 -1.54%, -1.51 % and 3.42%, respectively, when calculated against the $Cardura^{TM}$ tablet. The powers $(1-{\beta})$ for $AUC_t,\;C_{max}\;and\;T_{max}$ were all more than 99.00%. Minimum detectable differences $(\Delta)$ at ${\alpha}=0.05\;and\;1-{\beta}=0.8$ were all less than 20% (e.g., 12.73%, 12.84% and 13.01% for $AUC_t,\;C_{max}\;and\;T_{max}$, respectively). The 90% confidence intervals were all within :${\pm}20%$ (e.g., $-8.97{\sim}5.90,\;-9.01{\sim}6.00\;and\;-4.16{\sim}11.05\;for\;AUC_t,\;C_{max}\;and\;T_{max},\;respectively)$. All of the above para- meters met the criteria of KFDA for bioequivalence, indicating that $Cardil^{TM}$ tablet is bioequivalent to $Cardura^{TM}$ tablet.

• Journal of Pharmaceutical Investigation
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• v.30 no.3
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• pp.213-218
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• 2000

Ondansetron is a potent, highly selective 5-hydroxytryptamine3(5-HT3) receptor- antagonist, for the management of nausea and vomiting induced by cytotoxic chemotherapy and radiography, and the treatment of post-operative nausea and vomiting. The purpose of the present study was to evaluate the bioequivalence of two ondansetron tablets, $Zofran^{TM}$, (Glaxo Wellcome Korea Ltd.) and Hana ondansetron (Hana Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers, $23.56{\pm}1.79$ year in age and $67.35{\pm}8.35\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 8 mg of ondansetron was orally administered, blood was taken at predetermined time intervals and the concentrations of ondansetron in serum were determined using HPLC with UV 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 7.53%, -0.23% and -3.92%, respectively when calculated against the $Zofran^{TM}$, tablet. The powers $(1-{\beta})$ for $AUC_t,\;C_{max}\;and\;T_{max}$ were above 99.00%, above 99.00% and 84.99%, respectively. Minimum detectable differences $(\Delta)\;at\;{\alpha}=0.1\;and\;1-{\beta}=0.8$ were all less than 20% (e.g., 12.25%, 10.88% and 18.37% for $AUC_t,\;C_{max}\;and\;T_{max}$, respectively). The 90% confidence intervals were all within ${\pm}20%$ (e.g., $-0.70{\sim}15.76,\;-7.53{\sim}7.08\;and\;-16.27{\sim}8.42\;for\;AUC_t,\;C_{max}\;and\;T_{max}$, respectively). All of the above parameters met the criteria of KFDA for bioequivalence, indicating that Hana ondansetron tablet is bioequivalent to $Zofran^{TM}$, tablet.