• 한국임상약학회지
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• 제14권2호
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• pp.85-90
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• 2004

Bisoprolol, one of the $\beta_1-adrenorecepter$ antagonist, has been used for the treatment of mild to moderate essential hypertension anti stable angina pectoris. The oral bloavailability of bisoprolo1 is high $(90\%)$ and the drug has a long elimination half-life, $9{\sim}12\;hr$, which allows once-daily administration. The bioequivalence of two bisoprolol preparations was evaluated according to the guidelines of Korea Food & Drug Administration (KFDA). The test product was Concor $tablet^{(R)}$ made by Newgenpharm and the reference product was Monocor $tablet^{(R)}$ made by Wyeth Korea. Twenty healthy male subjects, 23.8 (21-30) years old and 03.8(52-92) kg, were randomly divided into two groups and a randomized $2\times2$ cross-over study was employed. After two tablets containing 10 mg bisoprolol hemifumarate were orally administered, blood was taken at predetermined time intervals and the concentration of bisoprolol in plasma was determined using an HPLC method with fluorescence detector. Two pharmacokinetic parameters, $AUC_t\;and\;C_{max}$ were calculated and analyzed statistical]y for the evaluation of bioequivalence of the two products. Analysis of variance was carried out using logarithmically transformed parameter values. The $90\%$ confidence intervals of $AUC_t\;and\;C_{max}$ were log $0.95{\sim}1og\;1.04\;and\;1og\;0.96{\sim}1og\;1.07,\;respectively.$ These values were within the acceptable bioequivalence intervals of log $0.8{\sim}log\;1.23$. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating that Concor tablet is bioequivalent to Monocor tablet.

• 동의생리병리학회지
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• 제27권4호
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• pp.453-459
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• 2013

The objective of this study was to evaluate the single oral dose toxicity of Polygalae Radix (PR) in male and female mice. PR extract (yield = 18.6%) was administered to ICR mice as an 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 (2009-116, 2009). Animals were monitored for the mortality and the changes in body weight, clinical signs and gross observation during 14 days after dosing. Upon necropsy, organ weight and histopathology of 14 principal organs were examined. It was observed that there were no mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principal organs related to PR extract up to 2,000 mg/kg. Therefore, 50% lethal dose ($LD_{50}$) and approximate LD of PR aqueous extracts after single oral treatment in female and male mice were considered over 2000 mg/kg the limited dosages recommended by KFDA Guidelines, respectively.

• 동의생리병리학회지
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• 제25권1호
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• pp.100-108
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• 2011

The object of this study was two. One was if Polygonati Rhizoma preparata had a benzo(a)pyrene, the other was to evaluate the single dose toxicity of 9 repetitive steaming and fermenting processed Polygonati Rhizoma, dried root parts of Polygonati Rhozoma preparata extract, in male and female mice. We measured a content of benzo(a)pyrene in Polygonati Rhozoma preparata using a method with HPLC/FLD. And for single dose toxicity, aqueous extracts of Polygonati Rhozoma preparata (EPP; Yield = 35.4 %) was administered to female and male ICR mice as an 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 the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy; organ weight and histopathology of 12 principle organs were examined. As results, we could not find any mortality, clinical signs, and changes in the body and organ weight except for slight soft feces sporadically detected in EPP treated male mice at 1 day after administration. In addition, no EPP-treatment related abnormal gross findings and changes in histopathology of principle organs were detected except for some sporadic accidental findings. The results obtained in this study suggest that benzo(a)pyrene was not existed in Polygonati Rhozoma preparata and the 50% lethal dose and approximate lethal dose of EPP aqueous extracts in both female and male mice were considered as over 2,000 mg/kg, the limited highest dosage recommended by KFDA Guidelines. However, it also observed that the possibilities of digestive disorders, like soft feces when administered over 500 mg/kg of EPP aqueous extracts in the present study.

• Biomolecules & Therapeutics
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• 제6권4호
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• pp.423-428
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• 1998

Aceclofenac is an orally effective non-steroidal anti-inflammatory agent of the phenylacetic acid derivative. Bioequivalence study of two aceclofenac preparations, the test drug (Senafe $n_{R}$: Daewon Phar-maceutical Company) and the reference drug (Airta $l_{R}$: Daewoong Pharmaceutical Company), was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Sixteen healthy male volunteers, 24$\pm$4 years old and 63.9$\pm$6.9 kg of body weight in average, were divided randomly into two groups and administered the drug orally at the dose of 100 mg as aceclofenac in a 2$\times$2 crossover study. Plasma concentrations of aceclofenac were monitored by HPLC method for 12 hr after administration. AU $Co_{-12h}$ (area under the plasma concentration-time curve from initial to 12 hr) was calculated by the linear trapezoidal method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{msx}$) were compiled directly from the plasma drug concentration-time data. Student's t-test indicated no significant differences between the formulations in these parameters. Analysis of variance (ANOVA) revealed that there are no differences in AU $Co_{12h}$, $C_{max}$ and $T_{max}$ between the formulations. The apparent differences between the formulations were far less than 20% (e.g., 0.25, 0.01 and 7.32 for AU $Co_{-12h}$, $C_{max}$. and $T_{max}$, respectively). Minimum detectable differences (%) between the formulations at $\alpha$=0.05 and 1-$\beta$=0.8 were less than 20% (e.g., 14.65, 12.47 and 15.46 for AU $Co_{-l2h}$, $C_{max}$ and $T_{max}$, respectively). The 90% confidence intervals for these parameters were also within $\pm$ 20% (e.g.,-10.19~10.68, -8.87~8.89 and -3.69~ 18.33 for AU $Co_{-12h}$, $C_{msx}$ and $T_{max}$, respectively). These results satisfy the bioequivalence criteria of KFDA guidelines, indicating that two formulations of aceclofenac are bioequivalent.quivalent.ivalent.ent.t.ent.

• 한국임상약학회지
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• 제16권1호
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• pp.34-39
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• 2006

Fexofenadine, one of selective histamine $H_1$ receptor antagonists, has been used for the treatment of seasonal allergic rhinitis and chronic idiopathic urticaria. The bioequivalence of two fexofenadine hydrochloride preparations, containing 120 mg fexofenadine hydrochloride, was evaluated according to the guidelines of Korea Food & Drug Administration(KFDA). The test product was Hanmi Fexofenadine Hydrochloride Tablet $120mg^{(R)}$ made by Hanmi Pharm. Co. and the reference product was Allegra Tablet $120mg^{(R)}$ made by Handok Parmaceuticals Co.. Twenty healthy male subjects were randomly divided into two groups and a $2{\times}2$ cross-over study was employed. After one tablet was orally administered, blood was taken at predetermined time intervals and the concentration of fexofenadine in plasma was determined using a validated HPLC method with fluorescence detector. Two pharmacokinetic parameters, $AUC_t\;and\;C_{max}$, were calculated and analyzed statistically for the evaluation of bioequivalence of the two products. Analysis of variance was carried out using logarithmically transformed parameter values. The 90% confidence intervals of $AUC_t\;and\;C_{max}$ were log $0.844{\sim}log$ 1.149 and log $0.833{\sim}log$ 1.109, respectively. These values were within the acceptable bioequivalence intervals of log 0.8 to log 1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating that Hanmi Fexofenadine Hydrochloride Tablet 120 mg is bioequivalent to Allegra Tablet 120 mg.

• Journal of Pharmaceutical Investigation
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• 제36권1호
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• pp.53-58
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• 2006

Fexofenadine, one of selective histamine $H_1$ receptor antagonists, has been used for the treatment of seasonal allergic rhinitis and chronic idiopathic urticaria. The bioequivalence of two fexofenadine hydrochloride preparations, containing 180 mg fexofenadine hydrochloride, was evaluated according to the guidelines of Korea Food & Drug Administration (KFDA). The test product was Hanmi Fexofenadine Hydrochloride $Tablet^{\circledR}$ made by Hanmi Pharm. Co. and the reference product was Allegra $Tablet^{\circledR}$ made by Handok Parmaceuticals Co.. Twenty healthy male subjects were randomly divided into two groups and a $2\;{\time}\;2$ cross-over study was employed. After one tablet was orally administered, blood was taken at predetermined time intervals and the concentration of fexofenadine in plasma was determined using a validated HPLC method with fluorescence detector. Two pharmacokinetic parameters, $AUC_t$ and $C_{max}$, were calculated and analyzed statistically for the evaluation of bioequivalence of the two products. Analysis of variance was carried out using logarithmically transformed parameter values. The 90% confidence intervals of $AUC_t$ and $C_{max}$ were $log\;0.822{\sim}log \;1.142$ and $log\;0.848{\sim}log\;1.172$, respectively. These values were within the acceptable bioequivalence intervals of log 0.8 to log 1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating that Hanmi Fexofenadine Hydrochloride Tablet is bioequivalent to Allegra Tablet.

• 약학회지
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• 제45권2호
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• pp.220-226
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• 2001

A bioequivalence study of Lovastati $n^{TM}$ tablets (Dong Sung Pharmaceutical Co., Korea) to Mevaco $r^{TM}$ tablets (Choong Wae Pharmaceutical Co., Korea) was conducted according to the guidelines (No. 98-56) of Korea Food and Drug Administration (KFDA). Each tablet contained 20 mg of lovastatin. Eighteen healthy Korean male subjects received each formulation at a lovastatin dose of 80 mg (i.e., four tablets) in a 2 $\times$ 2 crossover study. There was a washout period of a week between the dose of the two formulations. Plasma concentrations of lovastatin acid were monitored by a GC/MS method for over a period of 12hr after each administration. The area under the plasma concentration-time curve from time zero to 12hr (AUC) was calculated by a linear trapezoidal method. The maximum plasma drug concentration ( $C_{max}$) and the time to reach $C_{max}$ ( $T_{max}$) were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) of these parameters revealed that there are no differences in AUC and $C_{max}$ between the formulations. The apparent differences between the formulations in these parameters were 4.87 and 8.03% for AUC and $C_{max}$, respectively. Minimum detectable differences (%) at $\alpha$=0.1 and 1-$\beta$=0.8 were 17.84 and 15.36% for AUC and $C_{max}$ respectively. The 90% confidence intervals were -15.30~5.56 and -17.02-0.95% for AUC and $C_{max}$, respective1y. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating Mevaco $r^{TM}$ tablets and Dong Sung Lovastati $n^{TM}$ tablets are bioequivalent.ivalent.ent.alent.ent.

• 통합자연과학논문집
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• 제4권4호
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• pp.315-322
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• 2011

This study was performed to investigate the current regulatory guidances of safety and efficacy evaluation for the approval of stereoisomeric drugs in Korea and US. According to the regulatory guidelines in major countries (EU, Canada, US), the important categories for the development of stereoisomeric drugs are classified as 1) development of a single enantiomer as a new active substances 2) development of a racemate as a new active substance 3) development of a new single enantiomer from an approved racemate. For this study, domestic regulatory documents for current guidelines of stereoisomeric drugs were investigated. Also four typical stereoisomeric drugs for three categories were chosen to investigate the new drug submission documents of KFDA and FDA for the safety and efficacy evaluation of stereoisomeric drugs. It is expected that these comparative results between KFDA and FDA will be useful for the safety and efficacy for the regulatory approval of stereoisomeric drugs in Korea.

• 한국임상약학회지
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• 제10권1호
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• pp.25-29
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• 2000

Bioequivalence of cisapride-containing $Cisaplus^{(R)}$ tablets (Daewoong Co.) to reference $Prepulsid^{(R)}$ tablets (Janssen Co.) was evaluated according to the guidelines of Korea Food and Drug Administration (KFDA). Sixteen healthy volunteers were divided randomly into two groups and administered orally at a cisapride dose of 10 mg in a $2\times2$ crossover design. There was a 1-week washout period between the treatments. Blood samples were taken at predetermined time intervals for 48 hr and the plasma cisapride concentrations were determined by an HPLC with UV detector. The area under the plasma drug concentration-time curve (AUC) was caltulated from time zero to the last sampling time by a linear trapezoidal method. The maximum observed plasma drug concentration ($C_{max}$) and the time to $C_{max}\;(T_{max})$ were estimated directly from the drug concentration-time data. Analysis of variance (ANOVA) showed that the apparent differences for AUC, $C_{max}\;and\;T_{max}$ were $-7.52\%,\;-8.91\%\;and\;-15.55\%$, respectively. The minimum detectable differences for AUC, $C_{max}\;and\;T_{max}$ between formulations were $14.52\%,\;11.57\%\;and\;28.00\%$ respectively, at $\alpha=0.05\;and\;1-\beta=0.8\;levels.\;The\;90\%$ confidence intervals for AUC, $C_{max}\;and\;T_{max}\;were\;-16.00\sim0.97\%,\;-15.67\sim-2.15\%\;and\;-31.88\%\sim0.84\%$, respectively. These results satisfy the bioequivalence criteria of KFDA guidelines, indicating that the two formulations of cisapride are bioequivalent.

• Journal of Pharmaceutical Investigation
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• 제34권6호
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• pp.499-504
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• 2004

Paroxetine, a potent and selective serotonine reuptake inhibitor, has been used for the treatment of depression, obsessive-compulsive disorder, panic disorder and social phobia. The bioequivalence of two paroxetine preparations was evaluated according to the guidelines of Korea Food & Drug Administration (KFDA). The test product was Samchully Paroxetine $tablet^{\circledR}$ made by Samchully Pharm. Co. and the reference product was Seroxat $tablet^{\circledR}$ made by GlaxoSmithKline. Twenty healthy male subjects, $22.4{\pm}2.6$ years old and $63.8{\pm}4.2\;kg$, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 20 mg paroxetine was orally administered, blood was taken at predetermined time intervals and the concentration of paroxetine in plasma was determined using a validated HPLC method with fluorescence detector. Two pharmacokinetic parameters, $AUC_t$ and $C_{max}$, were calculated and analyzed statistically for the evaluation of bioequivalence of two products. Analysis of variance was carried out using logarithmically transformed parameter values. The 90% confidence intervals of $AUC_t$ and $C_{max}$ were log 0.84-log 1.16 and log 0.85-log 1.14, respectively. These values were within the acceptable bioequivalence intervals of log 0.8 to log 1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating that Samchully Paroxetine tablet is bioequivalent to Seroxat tablet.