• 한국임상약학회지
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• 제12권1호
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• pp.22-28
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• 2002

Aceclofenac, 2-[(2',6'-dichlorphenyl)amino]phenylacetoxiacetic acid, is a new nonsteroidal anti-inflammatory drug that belongs to the family of phenylacetic acids. It shows good tolerance and potent analgesic/antiinflammatory properties, and acts on cartilaginous chondriocytes, stimulating their repair mechanism. The purpose of the present study was to evaluate the bioequivalence of two aceclofenac products, $Airtal^{TM}$ tablet (Daewoong Pharmaceutical Co.) and $Acer^{TM}$ capsule (Kyungdong Pharmaceutical Co.), according to the guideliner of Korea Food and Drug Administration (KFDA). The aceclofenac release from the two aceclofenac products in vitro was tested using KP VII Apparatus II method at pH 7.8 dissolution media. Sixteen normal male volunteers, $23.13\pm2.03$ years in age and $66.33\pm7.08$ kg in body weight, were divided into two groups and a randomized $2\times2$ cross-over study was employed. After one tablet or capsule containing 100 mg of aceclofenac was orally administered, blood was taken at predetermined time intervals and the concentrations of aceclofenac in serum were determined using HPLC with UV detector. The dissolution profiles of the two aceclofenac products were very similar at pH 7.8 dissolution media. 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. The results showed that the differences in $AUC_t,\;C_{max}\;and\;T_{max}$ between two products were $6.50\%,\;-1.06\%\;and\;11.96\%$ respectively, when calculated against the $Airtal^{TM}$ tablet. The powers $(1-\beta)\;for\;AUC_t,\;C_{max}\;were\;89.82\%\;and\;82.84\%$, respectively. Minimum detectable differences $(\Delta)\;at\;\alpha=0.05\;and\;1-\beta=0.8$ were less than $20\%\;(e.g.,\;17.51\%\;and\;19.30\%\;for\;AUC_t,\;C_{max}$, ). The $90\%$ confidence intervals were within $\pm20\%\;(e.g.,\;-3.73\%\sim16.73\%\;and\;-12.34\%\sim10.22\%\;for\;AUC_t,\;C_{max},\;respectively)$. Two parameters met the criteria of KFDA for bioequivalence, indicating that $Acer^{TM}$ capsule is bioequivalent to $Airtal^{TM}$ tablet.

• 한국임상약학회지
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• 제15권1호
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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.

• 감성과학
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• 제22권3호
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• pp.3-20
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• 2019

가상현실 기술이 발전하면서 다양한 영역에서 여러 목적으로 활용되고 있다. 하지만 사용자로부터 메스꺼움, 어지러움 등과 같은 멀미 증상에 대한 부작용도 함께 보고되고 있다. 이런 멀미 증상을 사이버멀미라고 말하며, 사용자에게 불편을 야기시켜 불쾌감과 스트레스와 같은 부정적 영향을 줄 수 있으며, 현재 사이버멀미의 발생 원인과 해결책에 관한 공식적인 표준이 없다. 본 연구에서는 이런 한계점을 극복하기 위해 정량적, 객관적 사이버멀미 평가법을 제안하였다. 10명의 20대 남성 대상으로 이동과 회전을 하는 가상현실을 경험하게 하면서 128채널의 뇌파를 측정하였다. 11개 영역에서 Delta와 Alpha 상대 파워를 계산하고, ROC curve를 통해 area under the ROC curve (AUC)가 가장 높은 값을 가지는 다중회귀모형을 도출하였다. 이렇게 도출한 다중회귀모형은 11개의 설명변수로 피험자가 응답한 사이버멀미의 정도와 비교하여 95.1 % (AUC = 0.951)의 정확성으로 사이버멀미를 구분하는 것이 가능함을 알 수 있었다. 이러한 결과를 정리하면 본 연구에서는 128 채널의 뇌파를 통해 멀미에 대한 객관적 반응을 확인하였으며, 뇌의 특정부위에서 반응이 있는 것으로 나타났다. 본 연구 결과와 분석법을 활용하면 추후 사이버멀미 관련 연구에 도움이 될 수 있을 것으로 기대된다.

• 약학회지
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• 제47권4호
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• pp.239-243
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• 2003

Metformin is an oral antihyperglycemic agent used in the therapy of noninsulin-dependent diabetes mellitus and does not cause hypoglycemia at the therapeutic dose. The purpose of the present study was to evaluate the bioequivalence of two metformin hydrochloride tablets, Glucophage tablet (DaeWoong Pharmaceutical Co., reference drug) and Dybis tablet (Shinpoong Pharmaceutical Co., test drug), according to the guidelines of Korea Food and Drug Administration(KFDA). Twenty-four normal volunteers, 26.6$\pm$4.01 years in age and 60.6$\pm$9.80 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 metformin hydrochloride was orally administered, blood was taken at predetermined time intervals and the concentrations of metformin hydrochloride in serum were determined using HPLC with UV detector. The pharmacokinetic parameters such as AUCt, Cmax and Tmax were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in AUCt, Cmax and Tmax between two products were -1.05％, -6.76％ and -4.51％, respectively, when calculated against the reference drug. The 90％ confidence intervals using logarithmically transformed data were within the acceptance range of log0.8$\leq$$\delta$$\leq$log1.25 (e.g., log0.9082$\leq$$\delta$$\leq$log1.0906 and log0.8188$\leq$$\delta$$\leq$log1.0392 for $AUC_{t}$ and $C_{max}$, respectively). The 90％ confidence intervals using untransformed data was within $\pm$20％ (e.g., -17.66％$\leq$$\delta$$\leq$8.63％ for $T_{max}$). All parameters met the criteria of KFDA for bioequivalence, indicating that Dybis tablets (Shinpoong Pharmaceutical Co.) is bioequivalent to Glucophage tablets (DaeWoong Pharmaceutical Co.).

• 자원환경지질
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• 제55권2호
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• pp.127-135
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• 2022

Excessive presence of As level in groundwater is a major health problem worldwide. In the Red River Delta in Vietnam, several million residents possess a high risk of chronic As poisoning. The As releases into groundwater caused by natural process through microbially-driven reductive dissolution of Fe (III) oxides. It has been extracted by Red River residents using private tube wells for drinking and daily purposes because of their unawareness of the contamination. This long-term consumption of As-contaminated groundwater could lead to various health problems. Therefore, a predictive model would be useful to expose contamination risks of the wells in the Red River Delta Vietnam area. This study used four machine learning algorithms to predict the As probability of study sites in Red River Delta, Vietnam. The GBM was the best performing model with the accuracy, precision, sensitivity, and specificity of 98.7%, 100%, 95.2%, and 100%, respectively. In addition, it resulted the highest AUC of 92% and 96% for the PRC and ROC curves, with Eh and Fe as the most important variables. The partial dependence plot of As concentration on the model parameters showed that the probability of high level of As is related to the low number of wells' depth, Eh, and SO₄, along with high PO₄^3- and NH₄⁺. This condition triggers the reductive dissolution of iron phases, thus releasing As into groundwater.

• Journal of Pharmaceutical Investigation
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• 제32권3호
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• pp.173-179
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• 2002

Solid dispersions of ipriflavone with PVP were prepared by a spray-drying method in order to improve the bioavailability. They were measured with scanning electron microscopy, differential scanning calorimetry, x-ray powder diffraction, and Fourier transform infrared spectroscopy to evaluate the physicochemical interaction between ipriflavone and PVP and study the correlation between these physicochemical characteristics and bioavailability. Ipriflavone exhibited crystallinity, whereas PVP was almost amorphous. The area of the endotherm $({\Delta}H)$ of freezer milled ipriflavone, freezer milled ipriflavone physically mixed with freezer milled PVP, and physically mixed ipriflavone with PVP was almost the same, whereas ${\Delta}H$ of the solid dispersed ipriflavone with PVP was much smaller than that of the other preparation types. Also, the crystallinity and the crystal size of ipriflavone in the solid dispersed ipriflavone with PVP were much smaller than those of the other preparation types. From the in vivo test, the AUC of the solid dispersed ipriflavone with PVP was approximately 10 times higher than that of the physically mixed ipriflavone with PVP. The solid dispersion using the spray-drying method with a water-soluble polymer, PVP, may be effective for the improvement of the bioavailability.

• Journal of Pharmaceutical Investigation
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• 제32권2호
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• pp.119-125
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• 2002

A rapid, selective and reproducible high-performance liquid chromatographic method has been developed for the determination of terazocin in human plasma. Terazocin plus the internal standard, prazocin hydrochloride, were extracted from alkalified plasma with tert-butylmethyl ether, back-extracted into 0.05% phosphoric acid. Fifty ${\mu}l-portions$ of extract were injected onto a octadecylsilane column and eluted with a mixture of acetonitrile, water and triethylamine (30 : 70 : 0.1 v/v, adjusted to pH 5.0 with dilute phosphoric acid) at a flow rate of 1.0 ml/min. The fluorescence intensity of column eluents was monitored at excitation wavelength of 250 nm and emission wavelength of 370 nm. No interference peaks were observed. The practical limit of quantitation was 5 ng/ml for terazocin. The average intraday and interday coefficients of variation were 4.15 and 3.54%, respectively. Also intraday and interday precisions over the range $5{\sim}60\;ng/ml$ were $0.49{\sim}2.92\;and\;0.38{\sim}5.12%$, respectively. The bioequivalence of two terazosin tablets, the $Hytrine^{\circledR}$ (Il Yang Pharmaceutical Co., Ltd.) and the $Teratonin^{\circledR}$ (Sam-A Pharmaceutical Co., Ltd.), was evaluated according to the guideline of Korea Food and Drug Administration (KFDA). Sixteen healthy male volunteers $(24.6{\pm}2.0\;years\;old)$ were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 2 mg of terazosin was orally administered, blood was taken at predetermined time intervals and the concentration of terazosin in plasma was determined with a HPLC method using spectrofluorometric detector. AUC was calculated by the linear trapezoidal method. $C_{max}\;and\;T_{max}$ were compiled from the plasma drug concentration-time data. Analysis of variance (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 the two preparations were 0.21 %, 5.53% and 8.82%, respectively. The powers $(1-{\beta})\;for\;AUC_t,\;C_{max}\;and\;T_{max}$ were >99%, 97.49%, and 33.26%, respectively. Minimum detectable differences $({\Delta},\;%)\;at\;{\alpha}=0.1\;and\;1-{\beta}=0.8$ and the 90% confidence intervals were all less than ${\pm}20%$ except for $T_{max}.\;AUC_t\;and\;C_{max}$ met the criteria of KDFA for bioequivalence, indicating that $Teratonin^{circledR}$ tablets are bioequivalent to $Hytrine^{circledR}$ tablets.

• 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.

• 한국임상약학회지
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• 제10권2호
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• pp.62-67
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• 2000

Terbinafine has a primary fungicidal action mediated by squalene epoxidase inhibition. Treated fungi accumulate squalene while becoming deficient in ergosterol, an essential component of fungal cell membranes. Bioequivalence of two terbinafine tablets, $Lamisil^{TM}$ (Novartis Korea Ltd., Seoul, Korea) and $Mycosil^{TM}$ (Daewon Pharmaceutical Co., Ltd., Seoul, Korea), 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 $Mycosil^{TM}\;or\;Lamisil^{TM}$ (125 mg terbinafine), blood samples were taken at predetermined time intervals and the serum terbinafine 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 $AUC_t,\;C_{max}\;and\;T_{max}$ between two tablets based on the $Lamisil^{TM}$ tablet were $-2.24\%,\;-7.68\%\;and\;2.92\%$, respectively. The powers %(1-\beta)\;for\;AVC_t,\;C_{max}\;and\;T_{max}\;were\;87.11\%,\;95.36\%\;and\;99.99\%$, 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 $Mycosil^{TM}$ tablet is bioequivalent to $Lamisil^{TM}$ tablet.

• Pediatric Infection and Vaccine
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• 제24권1호
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• pp.1-6
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• 2017

목적: 본 연구에서는 delta neutrophil index (DNI)가 신생아 균혈증을 예측하는 지표로서의 효용성을 다른 지표들과의 비교를 통해 알아보고자 하였다. 방법: 원주세브란스 기독병원 신생아 중환자실에 발열을 주소로 입원한 환아들과 입원 중 발열이 있었던 생후 31일 미만 환아 146명을 대상으로 혈액배양검사와 동시에 시행한 총 백혈구 수, 절대호중구수, DNI, 혈소판 수, C-반응단백(C-reactive protein, CRP)에 대하여 분석하였다. 결과: 균혈증이 있었던 환아 77명의 평균 재태주수는 38.74주, 출생 체중은 3.20 kg였다. 대조군의 평균 재태주수는 33.34주, 출생 체중은 2.20 kg였다. 균혈증의 원인은 Staphylococcus aureus (22명), Staphylococcus epidermidis (18명), Streptococcus agalactiae (8명) 등이었다. DNI와 CRP만이 재태주수와 출생 체중 보정 후 균혈증과 연관성을 보여 area under the ROC curve를 조사하였고 DNI 0.70, CRP 0.68이었다. 결론: DNI는 신생아 균혈증을 예측하는 데 효과적인 지표이다. 다른 인자들과 함께 고려한다면 균혈증을 예측하는 데 더 도움이 될 것이다.