• Journal of Pharmaceutical Investigation
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• 제39권2호
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• pp.133-139
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• 2009

The purpose of the present study was to evaluate the bioequivalence of two pioglitazone HCl tablets, $Actos^{TM}$, tablets (Lilly Korea. Ltd., Korea) as a reference drug and $Piros^{TM}$, tablets (Reyon Pharm. Co., Ltd., Korea) as test drug, according to the guideline of Korea Food and Drug Administration (KFDA). Twenty-four healthy male Korean volunteers received one tablet containing pioglitazone HCl 15 mg in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Plasma concentrations of pioglitazone were monitored for over a period of 36 hr after administration by using a high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The area under the plasma concentration-time curve from time zero to 36 hr ($AUC_{0-36hr}$), maximum plasma drug concentration ($C_{max}$) and time to reach $C_{max}$ ($T_{max}$) were complied from the plasma concentration-time data. Analysis of variance (ANOVA) test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_{0-36hr}$ and $C_{max}$. The 90% confidence intervals of the $AUC_{0-36hr}$ ratio and the $C_{max}$ ratio for $Piros^{TM}$/$Actos^{TM}$. were log 0.8753-log 1.1286 and log 0.8669-log 1.1734, respectively. These values were within the acceptable bioequivalence intervals of log 0.80-log 1.25, recommended by KFDA. In all of these results, we concluded that the $Piros^{TM}$. tablet was bioequivalent to the $Actos^{TM}$. tablet, based on the rate and extent of absorption.

• Journal of Pharmaceutical Investigation
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• 제39권6호
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• pp.457-463
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• 2009

The purpose of the present study was to evaluate the bioequivalence of meloxicam capsule, $Mobic^{TM}$ capsule( Boehringer Ingelheim Ltd., Korea) as a reference drug and $Meloxifen^{TM}$ capsule (Kukje Pharma Ind. Co., Ltd., Korea) as a test drug, according to the guidelines of Korea Food and Drug Administration(KFDA). Thirty two healthy male Korean volunteers received capsule containing meloxicam 7.5 mg in a $2{\times}2$ crossover study. There was a one-week above washout period between the doses. Plasma concentrations of meloxicam were monitored for over a period of 72 hr after administration by using a high performance liquid chromatography-tandem mass spectrometer(LC-MS/MS). $AUC_t$(the area under the plasma concentration-time curve from time zero to 72 hr), $C_{max}$(maximum plasma drug concentration) and $T_{max}$(time to reach $C_{max}$) were complied 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 $AUC_t$ ratio and the $C_{max}$ ratio for $Meloxifen^{TM}/Mobic^{TM}$ were log 0.8605-log 0.9847 and log 0.9765-log 1.1503, respectively. These values were within the acceptable bioequivalence intervals of log 0.80-log 1.25, recommended by KFDA. In all of these results, we concluded that $Meloxifen^{TM}$ capsule was bioequivalent to $Mobic^{TM}$ capsule, based on the rate and extent of absorption.

• Nutrition Research and Practice
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• 제12권5호
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• pp.371-377
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• 2018

BACKGROUND/OBJECTIVES: Elevation of postprandial lipemia characterized by a rise in triglyceride (TG)-rich lipoproteins can increase the risk of atherogenesis. The objective of this study was to investigate postprandial lipemia response to a single dietary fat/sugar load test and monitor beneficial changes induced by the consumption of Platycodi radix (AP) beverage in healthy subjects. SUBJECTS/METHODS: A total of 52 subjects were randomly assigned to either placebo or AP beverage group with a high-fat shake in a randomized controlled crossover trial. Postprandial blood was collected at 0, 1, 2, 4, and 6 h and analyzed for TG and lipoprotein lipase mass. Inhibition of pancreatic lipase was determined in vitro. RESULTS: AP inhibited pancreatic lipase activity in vitro ($IC_{50}=5mg/mL$). Compared to placebo beverage, AP beverage consumption with a high-fat shake induced significant increase of plasma lipoprotein lipase mass (P = 0.0111, ${\beta}$ estimate = 4.2948) with significant reduction in very low-density lipoprotein (VLDL) TG concentration (P = 0.038, ${\beta}$ estimate = -52.69) at 6 h. Based on significant correlation between high-fat dietary scores MEDFICTS and postprandial TG responses in VLDL (P = 0.0395, r = 0.2127), subgroup analysis revealed that 6 h-postprandial VLDL TG response was significantly decreased by AP consumption in subjects with MEDFICTS ${\geq}40$ (P = 0.0291, ${\beta}$ estimate = -7214). CONCLUSIONS: AP beverage might have potential to alleviate postprandial lipemia through inhibiting pancreatic lipase activity and elevating lipoprotein lipase mass. Subgroup analysis revealed that subjects with high-fat dietary pattern could be classified as responders to AP beverage among all subjects.

• 생명과학회지
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• 제28권5호
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• pp.587-596
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• 2018

전 세계적으로 담배흡연자의 심혈관 위험 감소와 금연을 위한 대안으로 전자담배 이용이 급속하게 확산되고 있지만 니코틴을 포함한 잠재적 유해화합물을 함유한 전자담배의 심혈관 효과는 불분명하다. 본 연구는 전자담배 사용에 따른 심장자율신경조절 변화를 관찰하고 급성적인 교감신경흥분효과 및 부교감신경활동 저하 반응을 궐련담배 흡연과 직접 비교하려는 목적으로 수행되었다. 41명의 젊고 건강한 흡연남성들을 대상으로 자료 분석을 수행하였으며, 무작위 교차 설계에 의해 1주의 wash-out period를 적용하여 전자담배와 궐련담배 세션이 각각 실시되었다. 전자담배는 흡연 시를 포함한 흡연 후 5분까지, 궐련담배의 경우 흡연 시 및 흡연 후 최대 30분까지 교감신경활성화 및 부교감신경 감소가 관찰되었다. 두 제품 간 비교에서, 흡연 시를 포함한 흡연 후 30분 동안의 HRV 분석에서 전자담배는 궐련담배에 비해 비교적 교감신경흥분효과 및 부교감신경저하에서 적은 변화수준 및 단시간 변화를 제공하는 것으로 나타났다. 이상의 결과들은 비록 전자담배가 궐련담배에 비해 심장자율신경조절에서 상대적으로 완화된 효과를 제공한다고 할지라도 전자담배 내 니코틴 및 잠재적 위험요인들을 고려해 볼 때 급성적인 교감신경흥분작용 및 부교감신경의 저하를 야기함으로 과도한 사용에 주의가 요구된다.

• 한국임상약학회지
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• 제12권2호
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• pp.71-75
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• 2002

This study was carried out to compare the bioavailability of $Ceclex^{(R)}$ (test drug, cefaclor 250 mg/capsule) with that of $Ceclor^{(R)}$ (reference drug) and to estimate the pharmacokinetic parameters of cefaclor in healthy Korean adult. The bioavailability was examined on 20 healthy volunteers who received a single dose (250 mg) of each drug in the fasting state in a randomized balanced 2-way crossover design. After dosing, blood samples were collected for a period of 6hours. Plasma concentrations of cefaclor were determined using HPLC with UV detection. The pharmacokinetic parameters $(AUC_{0-6hr},\;C_{max},\;T_{max},\;AUC_{int},\;K_e,\;t_{1/2},\;Vd)$ F, and CL/F) were calculated with non-compartmental pharmacokinetic analysis. The ANOVA test was utilized for the statistical analysis of the $T_{max},\;log-transformed\;AUC_{0-6hr}\;log-transformed\;C_{max},\;t_{l/2},\;V_d/F$, and CL/F. The ratios of geometric means of AUC0-6hr and $C_{max}$ between test drug and reference drug were $103.2\%\;(6.74\;{\mu}g{\cdot}hr/ml\;vs\;6.53{\pm}g{\cdot}hr/ml)\;and\;100.4\%\;(4.85\;{\mu}g\ml\;vs\;4.82\;{\mu}g/ml)$, respectively. The $T_{max}$ of test drug and reference drug were $0.9\pm0.38\;hr\;and\;0.83\pm0.34$ hrs, respectively. The $90\%$ confidence intervals of mean difference of logarithmic transformed $AUC_{0-6h},\;and\;C_{max}$ were log $0.98{\sim}log$ 1.08 and log $0.88{\sim}log1.15$, respectively. It shows that the bioavailability of test drug is equivalent with that of reference drug. The estimated half-life of this study was longer $(1.21\pm0.27\;hrs\;vs\;0.5-1\;hr)$, the Vd/F was larger $(68.89\pm25.72L$ vs 24.9L), and the CL/F was higher $(38.62\pm7.09\;L/hr$ vs 24.9 L/hr) than the previously reported values.

• Journal of Ecology and Environment
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• 제43권2호
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• pp.104-116
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• 2019

Background: The composition of wild bird populations in temperate zones greatly varies depending on phenological changes rather than other environmental factors. Particularly, wild birds appearing in wetlands fluctuate greatly due to the crossover of species arriving for breeding during the summer and for wintering. Therefore, to understand the changes to species composition related to phenology, we conducted this basic analysis of populations to further the cause of the protection of wetland-dependent wild birds. Methods: It is wrong to simply divide a wild bird population investigation into seasons. This study identifies species composition and indicator species that change along with seasons. Wetlands to be surveyed are protected by natural monuments and wetland inventory and are in a state close to nature. In order to identify as many species as possible in wetlands, a survey was conducted in both shallow and deep wetlands. The water depth varied in these areas, ranging from 0.2 to 2.0 m, allowing for both dabbling and diving ducks to inhabit the area. Surveys were conducted using line-transect and distance sampling methods and were conducted at intervals of 2 weeks. The survey was conducted under the following three categories: the eco-tone and emergent zone, the submergent zone, and the water surface. The survey was conducted along a wetland boundary by observing wild birds. A PC-ord program was used for clustering, and the SAS program was used to analyze the changes in species composition. The data strongly indicates that day length is the main factor for seasonal migration periods, despite the fact that climate change and increasing temperatures are often discussed. Results and conclusions: The indicator species for determining seasons include migrant birds such as Ardea cinerea, Alcedo atthis, Anas penelope, and Poiceps ruficollis, as well as resident birds such as Streptopelia orientalis and Emberiza elegans. Importantly, increases in local individual counts of these species may also serve as indicators. The survey results of seasonal fluctuations in temperate zones shows that spring (April to June), summer (July to September), autumn (October), and winter (November to March) are clearly distinguishable, even though spring and summer seasons tend to overlap, leading to the conclusion that additional research could more clearly identify fluctuation patterns in species composition and abundance in the study area.

• 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.

• Journal of Pharmaceutical Investigation
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• 제35권2호
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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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• 제39권1호
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• pp.65-71
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• 2009

The aim of the present study was to evaluate the bioequivalence of two domperidone maleate tablets, Motilium-$M^{(R)}$ Tablet (Janssen Korea Ltd., reference product) and $Toriem^{(R)}$ Tablet (Daewon Pharm. Co., Ltd., test product). Domperidone was extracted by liquid-liquid extraction using tert-butyl methyl ether and separated in less than 3 min on $C_{18}$ reverse-phase column using an isocratic elution. A tandem mass spectrometer, as detector, was used for quantitative analysis in positive mode by a multiple reaction monitoring mode to monitor the m/z $426.1{\rightarrow}119.1$ and the m/z $837.4{\rightarrow}158.2$ transitions for domperidone and the internal standard (roxithromycin), respectively. Calibration curves, from $0.05{\sim}50$ ng/mL of domperidone, showed correlation coefficients (r) higher than 0.9941. Intra day and inter day precision (C.V. %) for quality control were ranged from 10.04 to 16.09% and from 10.87 to 18.69%, respectively. The lower limit of quantification (LLOQ) of domperidone was 0.05 ng/mL. The method described is precise and sensitive and has been successfully applied to the study of bioequivalence of domperidone in 24 healthy Korean volunteers. Twenty-four healthy male Korean volunteers received a single dose of each medicine ($2{\times}12.72\;mg$ domperidone maleate) in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Plasma concentrations of domperidone were monitored for over a period of 24 hr after the administration. $AUC_{0-t}$ (the area under the plasma concentration-time curve) was calculated by the linear trapezoidal rule. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. The 90% confidence intervals for the log transformed data were within acceptable range of log 0.8 to log 1.25 (e.g., $log\;0.92{\sim}log\;1.05$ for $AUC_{0-t}$, $log\;0.81{\sim}log\;1.05$ for $C_{max}$). The major parameters, $AUC_{0-t}$ and $C_{max}$ met the criteria of KFDA for bioequivalence indicating that $Toriem^{(R)}$ tablet is bioequivalent to Motilium-$M^{(R)}$ tablet.

• 인간행동과 음악연구
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• 제10권2호
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• pp.1-33
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• 2013

본 연구는 소아환자대상 최근의 음악치료 및 음악을 사용한 임상연구들에 대한 체계적인 문헌고찰(Systematic Review)을 위해 실시되었다. 이를 위해 13개 데이터베이스를 이용하여 2000년부터 2012년 사이에 영어로 발표 된 무작위 임상 및 교차설계 연구들을 자료로 수집하였고, 최초 검색 되었던 1023개의 논문 중 선정 및 제외기준에 따라 영어문헌 15건을 선별하였다. 선별 결과 연구 대상자는 1개월에서 만 18세까지의 아동 및 청소년으로 11명에서 150명 까지 표본크기가 다양했으며 전체 연구 참여자는 987명으로 집계되었다. 선별된 연구들은 음악요법 및 음악치료 연구로 분류되어 전반적인 유형, 연구절차와 방법론, 임상접근법, 측정도구 및 연구결과에 대해 체계적으로 분석되었다. 총 7건의 음악요법과 8건의 음악치료로 분류된 연구들은 7개영역의 종속변수를 36종류의 측정도구를 사용하여 측정하였는데 음악의 임상적 사용에 있어 음악의 선택, 종류 및 임상접근방법에 큰 차이가 있음이 나타났다. 연구절차와 방법론의 분석 결과 다수의 연구들이 주요 연구절차에 대한 기술이 충분치 않고 특히 무작위배정(Randomization), 배정순서 은폐(Allocation Concealment), 이중 또는 부분은폐(double or partial blinding) 및 참여자 감소율(Attrition Rate)과 같은 방법론적 표준에 미치지 못함이 도출되었다. 전반적인 연구결과가 통계적으로 유의하거나 긍정적 결과가 보고된 바 있으나, 연구 방법론적 문제들과 임상접근법들의 이질성으로 인해 그 결과가 편향에 의해 오염되거나 신뢰성에 문제가 있음을 확인할 수 있다. 그 결과 음악이 소아 환자들의 신체 및 사회 심리적 필요를 다루는 도구로 임상적 가치가 있음을 제안할 수는 있지만 이에 대한 과학적인 근거로서는 절차와 접근법이 보다 엄격하고 균일하여 추후 재현이 가능한 연구들이 다수 요구됨을 알 수 있다.