• Journal of Pharmaceutical Investigation
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• 제37권4호
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• pp.249-254
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• 2007

The purpose of the present study was to evaluate the bioequivalence of two baclofen tablets, $Baclan^{TM}$ tablet (Yooyoung Pharm. Co., Ltd., Seoul, Korea, reference drug) and Taepyungyang Baclofen tablet (Pacificpharma Corporation, Seoul, Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-four healthy male Korean volunteers received three tablets containing baclofen 10 mg in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Plasma concentrations of baclofen were monitored for over a period of 24 hr after the administration by using an LC-MS/MS. $AUC_t,\;C_{max}\;and\;T_{max}$ were compiled from the plasma concentration-time data. Analysis of variance (ANOVA) test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t\;and\;C_{max}$. The 90% confidence intervals of the $AUC_t$ and the $C_{max}$ for Taepyungyang $Baclofen/Baclan^{TM}$ were $log0.92{\sim}log1.06\;and\;log1.03{\sim}log1.22$, respectively. These values were within the acceptable bioequivalence intervals of $log0.80{\sim}log1.25$. It was concluded that Taepyungyang Baclofen tablet was bioequivalent to $Baclan^{TM}$ tablet, in terms of both rate and extent of absorption.

• 한국임상약학회지
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• 제11권2호
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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.

• 한국임상약학회지
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• 제10권1호
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• pp.13-18
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• 2000

The bioequivalence of two clarithromycin tablets, the $Klaricid^{TM}$ (Ciba-Geigy Korea Ltd.) and the $Pylocin^{TM}$ (Kyungdong Pharmaceutical Co., Ltd.), was evaluated according to the Korean Guidelines for Bioequivalence Test (KGBT 1998). Sixteen healthy male volunteers ($20\sim26$ years old) were randomly divided into two groups and a randomized $2\times2$ cross-over study was employed. After one tablet containing 250 mg of clarithromycin was orally administered, blood sample was taken at predetermined time intervals, and the concentrations of clarithromycin in serum were determined using high-performance liquid chromatographic method with electrochemical detector. The pharmaco-kinetic parameters (area under the concentration-time curve: $AUC_t$, maximum concentration; $C_{max}$ and time to maximum concentration; $T_{max}$) were calculated and analysis of variance (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 $-0.22\%,\;-0.48\%\;and\;-1.63\%$, respectively. The powers $(1-\beta)\;for\;AUC_t,\;C_{max}\;and\;T_{max}\;were\;99.07\%,\;88.15\%\;and\;99.99\%$, respectively. Detectable differences $(\Delta)\;and\;90\%$ confidence intervals ($\alpha$=0.10) were all less than $\pm20\%$ All the parameters above met the criteria of KGBT 1998, indicating that $Pylocin^{TM}$ tablet is bioequivalent to $Klaricid^{TM}$ tablet.

• Journal of Pharmaceutical Investigation
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• 제35권4호
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• pp.295-301
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• 2005

Famciclovir is an oral prodrug of the antiherpesvirus nucleoside analogue, penciclovir. In human, famciclovir is orally well absorbed and then undergoes extensive first pass metabolism to penciclovir and essentially no parent compound is recovered from plasma or urine. The purpose of the present study was to evaluate the bioequivalence of two famciclovir tablets, $Famvir^{TM}$ tablet 250 mg (Novartis Korea Ltd.) and Famcivir (Hanmi Pharmaceutical Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of famciclovir from the two famciclovir formulations in vitro was tested using KP VIII Apparatus II method with water. Twenty six healthy male subjects, $24.19{\pm}2.08$ years in age and $71.55{\pm}6.89$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single tablet containing 250 mg as famciclovir was orally administered, blood samples were taken at predetermined time intervals and the concentrations of penciclovir in serum were determined using HPLC with UV detector. The dissolution profiles of two formulations were similar at water. 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, $Famvir^{TM}$ tablet 250 mg, were -2.93, -8.02 and 10.47% 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 log0.8 to log1.25 (e.g., $log0.92{\sim}log1.01$ and $log0.85{\sim}log1.00$ for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Famcivir was bioequivalent to $Famvir^{TM}$ tablet 250 mg.

• 대한전기학회:학술대회논문집
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• 대한전기학회 2003년도 학술회의 논문집 정보 및 제어부문 B
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• pp.959-961
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• 2003

In this paper, we describe implemented DMAC (Direct Memory Access Controller) architecture on Altera's $Excalibur^{TM}$ that includes industry-standard $ARM922T^{TM}$ 32-bit RISC processor core operating at 200 MHz. We implemented DMAC based on AMBA (Advanced Micro-controller Bus Architecture) AHB (Advanced Micro-performance Bus) interface. Implemented DMAC has 8-channel and can extend supportable channel count according to user application. We used round-robin method for priority selection. Implemented DMAC supports data transfer between Memory-to-Memory, Memory-to-Peripheral and Peripheral-to-Memory. The max transfer count is 1024 per a time and it can support byte, half-word and word transfer according to AHB protocol (HSIZE signals). We implemented with VHDL and functional verification using $ModelSim^{TM}$. Then, we synthesized using $LeonardoSpectrum^{TM}$ with Altera $Excalibur^{TM}$ library. We did FPGA P&R and targeting using $Quartus^{TM}$. We can use implemented DMAC module at any system that needs high speed and broad bandwidth data transfers.

• Journal of Pharmaceutical Investigation
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• 제37권3호
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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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• 제37권4호
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• pp.255-261
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• 2007

A bioequivalence study of $Nimegen^{TM}$ soft capsule (Medica Korea Pharma. Co., Ltd.) to $RoAccutane^{(R)}$ soft capsule (Roche Korea Ind. Co., Ltd.) was conducted according to the guidelines of Korea Food and Drug Administration (KFDA). Thirty healthy male Korean volunteers received each medicine at the isotretinoin dose of 60 mg in a $2{\times}2$ crossover study. There was one week wash-out period between the doses. Plasma concentrations of isotretinoin were monitored by a high performance liquid chromatography (HPLC) for over a period of 48 hours after drug administration. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 48 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 $Nimegen^{TM}/RoAccutane^{(R)}$ were $log0.860{\sim}log0.98\;and\;log0.85{\sim}log1.00$, respectively. These values were within the acceptable bioequivalence intervals of $log0.80{\sim}log1.25$. Thus, our study demonstrated the bioequivalence of $Nimegen^{TM}\;and\;RoAccutane^{(R)}$ with respect to the rate and extent of absorption.

• 구강회복응용과학지
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• 제28권2호
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• pp.213-221
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• 2012

장기적인 칫솔질시 외부 stain 처리된 IPS e.max Press 도재의 색의 변화를 분광측색장치(SpectroShade$^{TM}$)를 이용하여 측정하고 비교함으로써 외부 stain의 색 안정성을 평가해 보고자 한다. IPS e.max Press LT ingots shade a1(Ivoclar Co.,Liechtenstein)를 사용하여 블록 형태의 시편을 제작하였으며 Orange, A, B, C, D shade로 외부 stain 처리 하였다. 칫솔질 기계를 이용하여 1년(11,000회), 2년(22,000회), 4년(44,000회), 6년(66,000회), 8년(88,000회) 치의 칫솔질 운동을 수평적으로 시행하였다. SpectroShade$^{tm}$ MICRO(MHT, Italy)를 이용하여 색조 변화를 측정하였다. 1년치(11,000회)의 칫솔질 연마 후 Orange shade에서 다른 4개의 shade보다 더 크게 색 차이가 나타났다. 그 후 칫솔질 횟수가 증가하여도, 외부 stain의 shade에 따른 색 차이의 변화는 통계적으로 유의성이 없었다. 칫솔질의 횟수의 증가에 따른 색 차이의 변화량은 일정한 증가나 감소의 경향을 보이지 않고 불규칙하였으며 통계학적으로 유의한 차이가 발견되지 않았다. 칫솔질이 IPS e.max Press 도재의 외부 stain의 변화에 크게 영향을 미치지 않으며 임상적으로도 외부 stain의 색 안정성이 인정된다고 생각된다. 추후 외부 stain에 영향을 미칠 수 있는 다른 요인들에 대한 연구도 필요하리라 사료된다.

• Journal of Pharmaceutical Investigation
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• 제34권1호
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• pp.49-55
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• 2004

To develop a aceclofenac soft capsule, four preparations with various solubilizers were prepared and their dissolution test was carried out. Among four preparations tested, a preparation with ethanolamine was selected as a formula of aceclofenac soft capsule (Clanza $S^{TM}$), since it showed the fastεst dissolution rate. Bioequivalence of aceclofenac tablet, $Airtal^{TM}$ (Dae-Woong Pharmaceutical Co., Ltd.) and aceclofenac soft capsule, Clanza $S^{TM}$ (Korea United Pharmaceutical Co., Ltd.) was evaluated according to the guideline of KA Fourteen normal male volunteers (age 20 - 25 years old) were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After oral administration of one tablet or capsule containing 100 mg of aceclofenac, blood was taken at predetermined time intervals and the concentration of aceclofenac in plasma was determined with an HPLC method under UV detector The pharmacokinetic parameters ($C_{max}$ and $AUC_t$) were calculated and ANOVA was utilized for the statistical analysis of parameters using logarithmetically transformed $AUC_t$, $C_{max}$ and $T_{max}$. The results showed that the differences in $AUC_t$, $C_{max}$ and $T_{max}$ between Aral tablet and Clanza soft capsule were 2.89%, 0.18% and 43.0%, 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(15) (e.g. log(0.81) -log(1.23) ad log(0.89) -log(1.4)) fo $AUC_t$ and $C_{max}$, respectively. Thus, the criteria of the KFDA guidelines for the equivalence was satisfied, indicating that Clanza $S^{TM}$ soft capsule is bioequivalent to$Airtal^{TM}$ tablet.

• Journal of Pharmaceutical Investigation
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• 제38권5호
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• pp.331-334
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• 2008

The objectives of this study were to formulate oral paclitaxel microemulsion and to compare the bioavailability of paclitaxel in the microemulsion formulation from the commercially available $Taxol^{(R)}$ formulation. Paclitaxel microemulsion was formulated with much less amount of Cremophor $EL^{TM}$ as compared with $Taxol^{(R)}$ to reduce severe adverse reactions produced by Cremophor $EL^{TM}$. The area under the plasma concentration-time curve from 0 hr to 24 hr ($AUC_{0-24}$), maximum plasma concentration ($C_{max}$), and relative bioavailability of palcitaxel microemulsion were increased as compared with $Taxol^{(R)}$ after oral administration. The time required to reach $C_{max}\;(T_{max})$ of palcitaxel microemulsion was significantly shorter than $Taxol^{(R)}$ following oral administration. These results suggest the faster intestinal absorption and the enhanced oral bioavailability of paclitaxel in the microemulsion formulation.