• Biomolecules & Therapeutics
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• 제11권1호
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• pp.65-71
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• 2003

Terbinafine is a synthetic allylamine that is available in an oral formulation and is used at a dosage of 250mg/day. It is used as an active antifungal agent and inhibits the fungal enzyme squalene epoxidase, which leads to the accumulation of the sterol squalene, which is toxic to the organism. The purpose of the present study was to evaluate the bioequivalence of two terbinafine tablets, Lamisil (Novartis Korea Ltd.) and Terbinex (C-TRI Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers, 26.00$\pm$2.57 year in age and 70.51$\pm$9.36 kg in body weight, were divided into two groups and a randomized 2${\times}$2 cross-over study was employed. After one tablet containing 125 mg of terbinafine was orally administered, blood was taken at predetermined time intervals and the concentrations of terbinafine in plasma were determined using HPLC with UV detector. Pharmacokinetic parameters such as AUC, $C_{max}$ 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, $C_{max}$ and $T_{max}$ between two tablets were －4.191％, 5.223％ and －25.720％, respectively when calculated against the Lamisil, tablet. The powers (1-$\beta$) for AUC, $C_{max}$ and $T_{max}$ were 81％, 87％ and below 60％, respectively. Minimum detectable differences(.il) at alpha=O.1 and 1-/3=0.8 were less than 20％ (e.g., 19.72％ and 17.77％ for AUC and $C_{max}$, respectively). But minimum detectable differences($\Delta$) at alpha=0.1 and 1-$\beta$=0.8 for $T_{max}$ were more than 20％ (e.g., 26.25％). The 90％ confidence intervals were within $\pm$20％ (e.g., －17.440∼9.06 and －6.713∼17.160 for AUC and $C_{max}$ respectively). But 90％ confidence intervals for $T_{max}$ were not within $\pm$20％ (e.g., －43.346∼8.083). Another ANOVA test was conducted for logarithmically transformed AUC and $C_{max}$. These results showed that there are no significant differences in AUC and $C_{max}$ between the two formulations: The differences between the formulations in these log transformed parameters were all for less than 20％ (e.g., －4.19％ and 5.22％ for AUC and $C_{max}$, respectively). The 90％ confidence intervals for the log transformed data were not the acceptance range of log 0.8 to log 1.25 in AUC but the acceptance range of log 0.8 to log 1.25 in $C_{max}$ (e.g., log 1.13∼log 1.50 and log 0.94-log 1.22 for AUC and $C_{max}$ respectively). The major parameters, AUC and $C_{max}$ met the criteria of KFDA for bioequivalence although $T_{max}$ did not meet the criteria of KFDA (1998 year) for bioequivalence, indicating that Onfran tablet is bioequivalent to Zofran tablet. But in another ANOVA test AUC did not meet the criteria of KFDA (2002) for bioequivalence but $C_{max}$ met the criteria of KFDA (2002 year) for bioequivalence.or bioequivalence.equivalence.equivalence.equivalence.

• Journal of Pharmaceutical Investigation
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• 제37권5호
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• pp.315-321
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• 2007

The purpose of the present study was to evaluate the bioequivalence of two lercanidipine hydrochloride tablets, Zanidip tablet (LG Life Sciences Ltd., Korea, reference drug) and Samchundang Lercanidipine tablet 10 mg (Sam Chun Dang Pharm. Co. Ltd., Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). After adding an internal standard (amlodipine maleate) to human serum, serum samples were extracted using hexan-isoamyl alcohol (100:1, v/v). Compounds were analyzed by liquid chromatography/tandem mass spectrometry. This method showed linear response over the concentration range of 0.05-20 ng/mL with correlation coefficient of 0.9999. The lower limit of quantitation using 0.5 mL of serum was 0.05 ng/mL which was sensitive enough for pharmacokinetic studies. Thirty healthy male Korean volunteers received each medicine at the lercanidipine hydrochloride dose of 20 mg in a $2\;{\times}\;2$ crossover study. There was a one-week washout period between the doses. Serum concentrations of lercanidipine were monitored by an LC/MS/MS fer over a period of 24 hr after the administration. $AUC_t$ (the area under the serum concentration-time curve from time 0 to 24 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (the maximum serum drug concentration) and $T_{max}$ (the time to reach $C_{max}$) were compiled from the serum 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 Samchundang Lercanidipine/Zanidip were log 0.9505-log 1.2258 and log 0.9987-log 1.2013, respectively. These values were within the acceptable bioequivalence intervals of log 0.80-log 1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating Samchundang Lercanidipine tablet 10 mg and Zanidip tablet are bioequivalent.

• 대한한의학방제학회지
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• 제14권1호
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• pp.141-167
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• 2006

The genotoxicity of water extract of Bojungikkeehapdaechilki-tang was tested by In Vitro Chromosome Aberration Test. Bacterial Reverse Mutation Assay and Micronucleus test according to OECD Guidelines and KFDA Guidelines. The obtained results were as follows : 1. Chromosome Aberration Test: In Vitro Chromosome Aberration Test of Bojungikkeehapdaechilki-tang extracts was carried out using cultured Chinese hamster lung cells in the presence and absence of metabolic activation system(S-9 mix). No significant changes in the number of aberrant metaphases having structural and number of aberrations were detected in Bojungikkeehapdaechilki-tang extracts treated groups. 2. Bacterial Reveres Mutation Assay: Bojungikkeehapdaechilki-tang extracts was evaluated for its potential to induce reverse mutation in the histidine auxotroph strains of Salmonella typhimurium such as TA100, TA1535, TA98 and TAl537 and the tryptophan auxotroph strain of Escherichia coli WP2 uvrA. No significant changes in the number of revertant colonies compared to its negative control were detected in Bojungikkeehapdaechilki-tang extracts treated groups against all 5 strains. 3. Micronucleus test: Micronucleus test of Bojungikkeehapdaechilki-tang extracts were performed using specific pathogen free 7-week old male ICR mouse. No significant changes in the number of micronucleated polychromatic erythrocytes among 2000 polychromatic erythrocytes compared to negative control were detected in all Bojungikkeehapdaechilki-tang extracts treated groups. In summarized above-mentioned results, it is concluded that Bojungikkeehapdaechilki-tang extracts have not genotoxicity against In Vitro Chromosome Aberration Test, Bacterial Reverse Mutation Assay and Micronucleus test.

• 약학회지
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• 제44권4호
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• pp.308-314
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• 2000

Logarithmic transformation of pharmacokinetic parameters is routinely used in bioequivalence studies based on pharmacokinetic and statistical grounds by the United States Food and Drug Administration (FDA), European Committee for Proprietary Medicinal Products (CPMP), and Japanese National Institute of Health and Science (NIHS). Although it has not yet been recommended by the Korea Food and Drug Administration (KFDA), its use is becoming increasingly necessary in order to harmonize with international standards. In the present study, statistical procedures for the analysis of a bioequivalence based on the log transformation and a related SAS procedure were demonstrated in order to aid the understanding and application. The AUC parameters used in this demonstration were taken from the previous bioequivalence study for two aceclofenac tablets, which were performed in a single-dose crossover design. Analysis of variance (ANOVA), statistical power to detect 20% difference between the tablets, minimum detectable difference and confidence intervals were all assessed following log-transformation of the data. Bioequivalence of two aceclofenac tablets was then estimated based on the guideline of FDA. Considering the international effort for harmaonization of guidelines for bioequivalence tests, this approach may require a further evaluation for a future adaptation in the Korea Guidelines of Bioequivalence Tests (KGBT).

• 한국정밀공학회지
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• 제33권11호
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• pp.937-941
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• 2016

Stand-alone cervical cage consists of a PEEK body, Ti plate, and screw, which are configured as a single-piece. Through a single operation, this implantable medical device is capable of completely fixing the cervical vertebral body. For example, instead of a plate, which is normally used, the intervertebral disc is removed and replaced with a cervical cage. It should be noted that in Korea, KFDA guidelines for a stand-alone cervical cage have not yet been suggested. Therefore, the aim of this study is to present the systematic study of the static compression test, static torsion test, dynamic compression test, and expulsion test. Further, the test method is designed to refer to the ASTM standard and relative literature.

• 응용통계연구
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• 제25권1호
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• pp.125-138
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• 2012

최근 들어 바이오시밀러에 대한 국내외 관심이 매우 증가하고 있다. 바이오시밀러가 오리지널 생물의약품과 효능과 안전성이 유사함을 보이기 위해서는 최종적으로 임상시험을 수행하여야 한다. 본 논문에서는 이러한 임상시험의 수행과 통계적 분석에 필요한 여러 방법들과 외국의 사례 그리고 관련된 가이드라인들을 살펴볼 것이다.

• 약학회지
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• 제55권3호
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• pp.185-194
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• 2011

Therapeutic duplication (TD) is frequently reported inappropriate drug use in healthcare settings in Korea. This study was aimed to develop TD criteria for psycho-nervous system drugs (KFDA classification 117 and 119). ATC classification was used to determine therapeutic and/or chemical similarities among the 93 ingredients reviewed. Clinical practice guidelines, textbooks and product labels were referenced for principles and evidences of possible drug combination usage. 16 groups that listed ingredients to be considered as TD were established and the criteria would be helpful to prevent TDs.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.242.2-242.1
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• 2003

The purpose of the present study was to evaluate the bioequivalence of two Erdosteine capsules, $Erdos^{TM}$(Dae Woong Pharmaceutical Co., Ltd.) and $Ersteine^{TM}$(Dae Won Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four normal male volunteers,23.88 ${\pm}$2.89 year in age and 68.50 ${\pm}$ 7.71 kg in body weight, were divided into two groups and radkomied 2${\times}$2 cross-over study was empolyed. Ater three capsules containing 300 mg of erdosteine per capsule were orally administered, blood was taken at predetermined time intervals and concentrations of erdostene I in plasma were determined using HPLC. (omitted)

• 한국임상약학회지
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• 제11권1호
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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.

• 대한한의학회지
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• 제26권2호
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• pp.32-51
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• 2005

Objectives: To study the effect of Artemisiae Capillaris Herba extracts, that have been used as oriental medicine to treat liver disease, on the perinatal and lactational n;)productive toxicity of SD rats when administered by oral lavage. Methods: Female SD rats were dosed from 6 days of gestation to 3 weeks postpartum. This was conducted in accordance with the recommendations of the KFDA Guidelines for Detection of Toxicity to Reproduction for Medicinal Products. Results: No Artemisiae Capillaris Herba extracts treatment-related changes in clinical signs, mortalities, implantation number, dead fetus number, loss rate of fetus, number of live young, survival rate of fetus, sex ratio of live young, external anomalies, pregnancy periods, viability index, lactational index, survival rate of litters at 4 days after birth or delivery index were demonstrated in any dosed levels in this study. However, the body weight and gains, food consumption and absolute organ weights of brain, adrenal glands, liver, spleen, kidney, ovaries and heart were significantly increased in 2000 or 1000mg/kg-dosing groups and the relative organ Weights of adrenal glands were significantly increased in 2,000mg/kg-dosing groups. Therefore, it was concluded that this increase was natural according to growth. Also, no changes of gross findings, clinical signs, mortalities, body weight and gains, physical development results, necropsy findings, organ weight, faculty test, open filed test and water-filled simple T-maze test, copulation, fertility, pregnancy indices, body weight and gains during gestation periods, necropsy findings, corpora lutea number, implantation number, implantation rate, dead fetus number, post-implantation loss rate, live young, post-implantation survival rate, sex ratio of live young, external anomalies and individual body weights of live young were demonstrated in any dosed levels in this study. Conclusions: It is considered that the NOAEL (No-Observed-Adverse-Effect Level) for perinatal and lactational reproductive toxicity of Artemisiae Capillaris Herba extracts was up to 2000mg/kg/day because no changes of other perinatal and lactational reproductive indices were demonstrated.