• Korean Journal of Clinical Pharmacy
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• v.15 no.1
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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.

• The Journal of Internal Korean Medicine
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• v.35 no.1
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• pp.37-49
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• 2014

Objectives & Methods : The objective of this study was to evaluate the single oral dose toxicity of Chongmyung-tang (CMT) in ICR mice. Korean traditional herbal prescription CMT has traditionally been used as a neuroprotective for treatment of learning disability and memory improvement. CMT, lyophilized aqueous extracts (yield=9.7%) were administered to female and male mice with oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines. Animals were monitored for mortality, changes in body weight, clinical signs and gross observation during 14 days after administration upon necropsy; organ weight and histopathology of 14 principle organs were examined. Results : We could not find any CMT extracts treatment related mortalities, clinical signs, changes in body and organ weight, or gross and histopathological observations against 14 principle organs up to 2,000 mg/kg in both female and male mice, except for some accidental sporadic findings which did not show any obvious dose-relations and most of which also demonstrated in both the female and male vehicle control mice in this experiments. Conclusions : Based on the results of this experiment, the 50% lethal dose ($LD_{50}$) and approximate lethal dose (ALD) of CMT extracts after single oral treatment in female and male mice can be considered to be over 2,000 mg/kg, and is likely to be safe in humans.

• Journal of Pharmaceutical Investigation
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• v.35 no.2
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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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• v.37 no.3
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• pp.197-203
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• 2007

A bioequivalence study of $Dilast^{TM}$ Capsule (Chong Kun Dang Pharma. Co., Ltd.) to $Ketas^{(R)}$ Capsule (Han Dok Pharma. Co., Ltd.) was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty eight healthy male Korean volunteers received each medicine at the ibudilast dose of 20 mg in a $2{\times}2$ crossover study. There was one week wash-out period between the doses. Plasma concentrations of ibudilast were monitored by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) 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 crossover design was properly performed. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for $Dilast^{TM}$ $Capsule/Ketas^{(R)}$ Capsule were $log0.93{\sim}log1.06$ and $log0.93{\sim}log1.11$, respectively. These values were within the acceptable bioequivalence intervals of $log0.80{\sim}log1.25$. Thus, our study demonstrated the bioequivalence of $Dilast^{TM}$ Capsule and $Ketas^{(R)}$ Capsule with respect to the rate and extent of absorption.

• Journal of Pharmaceutical Investigation
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• v.35 no.4
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• pp.303-308
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• 2005

The purpose of the present study was to evaluate the bioequivalence of two talniflumate tablets, SOMALGEN tablet (Kun Wha Pharm. Co., Ltd., Seoul, Korea, reference drug) and FLUTAL tablet (Kukje Pharm. Co., Ltd., Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four healthy male Korean volunteers received two tablets at the talniflumate dose of 740 mg in a $2{\pm}2$ crossover study. There was a one-week washout period between the doses. Plasma concentrations of niflumic acid were monitored by an HPLC-UV for over a period of 14 hr after the administration. $AUC_t$(the area under the plasma concentration-time curve from time zero to 14 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 $AUC_t$, $C_{max}$ and untransformed $T_{max}$. 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 SOMALGEN/FLUTAL were $log0.8510{\sim}log1.0318$ and $log0.9264{\sim}log1.0607$, respectively. These values were within the acceptable bioequivalence intervals of $log0.80{\sim}log1.25$. Taken together, our study demonstrated the bioequivalence of SOMALGEN and FLUTAL 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.32 no.3
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• pp.223-229
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• 2002

Metformin is an oral antihyperglycemic agent used in the therapy of noninsulin-dependent diabetes mellitus and does not cause hypoglycemia at the therapeutic dose. Its mechanism of action may involve an increased binding of insulin to its receptors and glucose uptake at the post-receptor level. The purpose of the present study was to evaluate the bioequivalence of two metformin tablets, Glucophage (Daewoong Pharmaceutical Co., Ltd.) and Glycomin (Ilsung Pharmaceuticals Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The metformin release from the two metformin tablets in vitro was tested using KP VII Apparatus II method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty four normal male volunteers, $23.75{\pm}1.96$ years in age and $68.77{\pm}10.41\;kg$ in body weight, were divided into two groups with a randomized $2{\times}2$ cross-over study. After one tablet containing 500 mg as metformin was orally administered, blood was taken at predetermined time intervals and the concentrations of metformin in serum were determined using HPLC with UV detector. Besides, the dissolution profiles of two metformin tablets were very similar at 떠1 dissolution media. The pharmacokinetic parameters such as $AVC_t,\;C_{max}\;and\;T_{max}$ were calculated. The ANOVA test was performed for the statistical analysis of the logarithmically transformed $AVC_t\;and\;C_{max}$, untransformed $T_{max}$. The results showed that the differences in $AVC_t,\;C_{max}\;and\;T_{max}$ between two tablets based on the Glucophage were 0.09%, 6.09% and -8.22%, respectively. There were no sequence effects between two tablets in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) $(e.g.,\;log(0.94){\sim}log(1.09)\;and \;log(1.01){\sim}log(1.15)$\;for\;AVC_t\;and\;C_{max},\;respectively)$, indicating that Glycomin tablet is bioequivalent to Glucophage tablet.

• Journal of Pharmaceutical Investigation
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• v.33 no.2
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• pp.135-140
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• 2003

Fluconazole is an orally active bis-triazole antifungal agent, which is used in the treatment of superficial and systemic candidiasis and in the treatment of cryptococcal infections in patients with the acquired immuno deficiency syndrome (AIDS). The purpose of the present study was to evaluate the bioequivalence of two fluconazole capsules, Diflucan (Pfizer Pharmaceuticals Korea Inc.) and Flucona (Korean Drug Pharmaceuticals Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The fluconazole release from the two fluconazole capsules in vitro was tested using KP VII Apparatus II method at 0.1 M hydrochloride dissolution media. Twenty normal male volunteers, $23.60{\pm}1.88$ years in age and $63.57{\pm}6.17\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After three capsules containing 50 mg as fluconazole was orally administered, blood was taken at predetermined time intervals and the concentrations of fluconazole in serum were determined using HPLC method with UV detector. The dissolution profiles of two fluconazole capsules were very similar at 0.1 M hydrochloride 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 using logarithmically transformed $AUC_t$ and $C_{max}$ and untransformed $T_{max}$. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between two capsules based on the Diflucan were 4.96%, 5.65% and -13.76%, respectively. There were no sequence effects between two capsules in these parameter. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) $(e.g.,\;log(1.01){\sim}log(1.08)\;and\;log(1.00){\sim}log(1.12)\;for\;AUC_t\;and\;C_{max},\;respectively)$, indicating that Flucona capsule is bioequivalent to Diflucan capsule.

• Journal of Pharmaceutical Investigation
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• v.28 no.3
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• pp.185-191
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• 1998

A bioequivalence study of the Loxipen tablets (Dae Wha Pharmaceutical Co., Korea) to the Loxonin tablets (Dong Hwa Pharmaceutical Co., Korea), formulations of sodium loxoprofen anhydrous 60 mg, was conducted. Sixteen healthy Korean male subjects received each formulation at the dose of 60 mg as sodium loxoprofen anhydrous in a $2{\times}2$ crossover study. There was a 2-week washout period between the dose. Plasma concentrations of loxoprofen were monitored by an HPLC method for over a period of 6 h after each administration. AUC (area under the plasma concentration-time curve from time zero to infinity) was calculated by the linear trapezoidal and extrapolation method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ $(time\;to\;reach\;C_{max})$ 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 apparent differences between the formulations in these parameters were all far less than 20% (i.e., 5.88, 7.81 and 6.09% for AUC, $C_{max}$ and $T_{max}$, respectively). Minimum detectable differences (%) at ${\alpha}=0.1$ and $1-{\beta}=0.8$ were all less than 20% difference in these parameters between the formulations were all over 0.8 (i.e., 15.81, 13.13 and 19.85 for AUC, $C_{max}$ and $T_{max}$, respectively). The 90% confidence intervals for these parameters were also within ${\pm}20%$ (i.e., $-16.52{\sim}4.77$, $-16.65{\sim}1,02$ and $-19.45{\sim}7.28%$ for AUC, $C_{max}$ and $T_{max}$, respectively). These results satisfy the bioequivalence criteria of the Korea Food and Drug Administration (KFDA) guidelines (No. 98-51). Therefore, these results indicate that the 2 formulations of loxoprofen are bioequivalent and, thus, may be prescribed interchangeably.

• Journal of Pharmaceutical Investigation
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• v.36 no.2
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• pp.131-136
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• 2006

The purpose of the present study was to evaluate the bioequivalence of two losartan tablets, $Cozaar^{TM}$ tablet (MSD Korea. Co., Ltd., Seoul, Korea, reference drug) and $Losartan^{TM}$ tablet (DaeWon Pharm. Co., Ltd., Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four healthy male Korean volunteers received two tablets at the losartan kalium dose of 100 mg in a $2\;{\time}\;2$ crossover study. There was a one-week washout period between the doses. Plasma concentrations of losartan were monitored by an LC-MS/MS for over a period of 12 hr after the 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 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 $Cozaar^{TM}/Losartan^{TM}$ were $log\;0.97{\sim}log\;1.12\;and\;log\;0.93{\sim}log\;1.23$, 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 $Cozaar^{TM}$ and $Losartan^TM$ with respect to the rate and extent of absorption.