• The Korean Journal of Applied Statistics
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• v.23 no.1
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• pp.139-150
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• 2010

In recent years, more generic drug products became available. The current regulation for assessing the bioequivalence of two drug formulations is based on the concept of average bioequivalence. This approach has been indicated to be insufficient for assessing switchability between two drug formulations and US FDA has adopted individual bioequivalence as one of the bioequivalence criterion since 2001. The US FDA recommends that individual bioequivalence be assessed based on $2\;{\times}\;4$ crossover design, while a $2\;{\times}\;3$ crossover design may be used as an alternative design to reduce the length and cost of the study. In this paper, a statistical procedure for assessment of individual bioequivalence under $3\;{\times}\;2$ crossover designs is proposed and some statistical points are discussed with $2\;{\times}\;3$ crossover design and $2\;{\times}\;3$ extra-reference design through simulation studies.

• Journal of the Korean Data and Information Science Society
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• v.28 no.4
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• pp.743-754
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• 2017

Assessing bioequivalence between original drug and generic drug is traditionally based on $2{\times}2$ crossover design. As bioequivalence trials for highly variable drugs are getting popular, the required sample size based on $2{\times}2$ crossover design would be very large, which might cause the ethical concerns. Regulatory agencies like EMA and MFDS recommended higher order crossover designs such as $2{\times}4$, $4{\times}2$ and $4{\times}4$ crossover designs. Alternatively, a $2{\times}3$ dual design may be recommended in terms of economical and ethical points of view in comparison with the $2{\times}4$ crossover design for highly variable drug. In this study, we consider some statistical characteristics of $2{\times}3$ dual design and propose statistical procedures for calculating sample size and assessing bioequivalence based on $2{\times}3$ dual design. We also discuss the proposed procedures from the perspective of newly revised bioequivalence guidance issued by MFDS.

• Journal of Pharmaceutical Investigation
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• v.28 no.4
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• pp.223-229
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• 1998

A computer program for personal computers, $K-BEtest^{\circledR}$, was developed to analyze bioequivalence data in accordance with Korean Guidelines for Bioequivalence Test (KGBT). This program is user-friendly, interactive, Hangul-compatible and supports $2{\times}2$ cross-over design as well as $2{\times}2$ Latin square design with various significance levels. This program is able to calculate AUC, $C_{max}$ and $T_{max}$ parameters from the blood drug concentration-time profile of individual subjects and evaluate the parameters statistically for the bioequivalence by ${\pm}20%$ rule, the F-test, the Non-centrality test and 90% confidence intervals. All procedures are supported with graphic interface, interactive menu and outputs in Korean. In this paper, two experimental data sets were analyzed by the program and detailed process was demonstrated. The $K-BEtest^{\circledR}$ program appears to be very effective for analyzing bioequivalence data and can be widely used with convenience and accuracy.

• Journal of Pharmaceutical Investigation
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• v.37 no.6
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• pp.329-338
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• 2007

The quality assurance issue of drug products is more important than the general product because it is highly related to the human health and life. In this reason, the regulatory guide lines have continuously been intensified all around the world. In order to achieve effective quality assurance and real-time product release (RTPR) of drug products, process analytical technology (PAT), which can analyze and control a manufacturing process, has been proposed from the United States. With the PAT process, we can obtain significant process features of materials, quality characteristics and product capabilities from a raw material to the final product in the real-time procedure. PAT can also be utilized to process validation using information system that can analyze the risk of drug products through out an entire product life-cycle. In this paper, we first offered a new concept for the off-line process design methods to prepare the improved quality assurance restrictions and a real-time control method by establishing an information system. We also introduced an automatic inspection system by obtaining surrogate variables based on drug product formulations. Finally, we proposed an advanced PAT concept using validation and feedback principles through out the entire life-cycle of drug product manufacturing processes.

• Journal of the Korean Statistical Society
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• v.35 no.3
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• pp.239-250
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• 2006

A $2{\times}2$ crossover design including carryover effect is considered for assessment of population bioequivalence of two drug formulations in a Bayesian framework. In classical analysis, it is complex to deal with the carryover effect since the estimate of the drug effect is biased in the presence of a carryover effect. The proposed method in this article uses uninformative priors and vague proper priors for objectiveness of priors and the posterior probability distribution of the parameters of interest is derived with given priors. The posterior probabilities of the hypotheses for assessing population bioequivalence are evaluated based on a Markov chain Monte Carlo simulation method. An example with real data set is given for illustration.

• Journal of the Korea Institute of Information and Communication Engineering
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• v.14 no.1
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• pp.145-155
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• 2010

In this paper, we suggest a fish drug domain ontology to show an associated information and hierarchy together through concept-relation and inference mechanism instead of keyword matching. First, we investigate competency questions from workers of fishery industry and then we derive concepts and terminologies. Next, we present a process of fish drug ontology modelling using Protege-OWL editor, which is an extension of Protege that supports the Web Ontology Language(OWL). Last, we suggest the user interface of semantic web-based fish drug information system to search easily associated informations of fish drug using this ontology. It is to provide an effective search method that fish disease manager, fish farmer, and students majoring in fisheries can confirm details of diseases, fish, and drug evaluations associated with fish drug within one screen without moving to another position.

• Bulletin of the Korean Chemical Society
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• v.32 no.3
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• pp.867-872
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• 2011

For the prolonged delivery and sustained release rates of low molecular weight drugs, poly(lactic-co-glycolic acid) (PLGA) microparticles containing the drug SKL-2020 have been investigated. On increasing polyvinyl alcohol (PVA) concentration (from 0.2% to 5%), the size of microparticles decreased (from $48.02{\mu}m$ to $10.63{\mu}m$) and more uniform size distribution was noticeable due to the powerful emulsifying ability of PVA. A higher drug loading (from 5% to 20%) caused a larger concentration gradient between 2 phases at the polymer precipitation step; this resulted in decreased encapsulation efficiency (from 34.19% to 25.67%) and a greater initial burst (from 61.71% to 70.05%). SKL-2020-loaded PLGA microparticles prepared with different fabrication conditions exhibited unique release patterns of SKL-2020. High PVA concentration and high drug loading led to an initial burst effect by rapid drug diffusion through the polymer matrix. Since PLGA microparticles enabled the slow release of SKL-2020 over 1 week in vitro and in vivo, more convenient and comfortable treatment could be facilitated with less frequent administration. It is feasible to design a release profile by mixing microparticles that were prepared with different fabrication conditions. By this method, the initial burst could be repressed properly and drug release rate could decrease.

• Bulletin of the Korean Chemical Society
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• v.30 no.7
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• pp.1463-1469
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• 2009

Eleven novel oxiranyl and thiiranyl phenolic compounds were synthesized as potential antitumor agents using epichlorohydrin and epithiohydrin in the presence of $K_2CO_3$. Cytotoxicities were found in range of I$C_{50}$ values of 2.5-14.8 $\mu$M, which was partially attributed to topoisomerase II inhibition. Bis-thiiranyl anthraquinone analog, 19 showed more cytotoxicity against MDA-MB-231 (breast cancer cell) and PC3 (prostate cancer cell) after 24 and/or 48 h and more potent topoisomerase II inhibitory activity than etoposide.

• YAKHAK HOEJI
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• v.57 no.1
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• pp.55-62
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• 2013

Objective: This study aims to assess the following issues - acquisition level in terms of the information on frequently used drugs of youth, access paths for the information, actual status of the use of drugs frequently used by youth, types of the used drugs, drug abuse among youth, and the consequent drawbacks. This study also takes aims at suggestion of correct role of pharmacists in consideration of drug abuse among youth. Methods: During the period from August 1, 2011 to October 31, 2012, a research design and a question development have been conducted. To the students of the schools that were randomly selected (elementary school's N=99, middle school's N=106, high school's N=115 and university's N=115), it was asked to complete given questionnaire from August 1, 2012 to August 31, 2012. During the period from September 1, 2012 to October 30, 2012, the questionnaires were collected back and the analysis and evaluation of them were carried out. Results: Drugs known to the respondents were a total of 115 different medicines and most of the drugs belonged to over-the-counter drugs. The most well known drug was pain reliever and the second most familiar drug was wound ointment. Most of the respondents found the drugs through direct use and advertisement. In everyday life, more than half of the respondents were using over-the-counter drugs as well as health supplements. The most commonly used drug was analgesic drug. It was showed that the respondents also frequently used the drugs for improving their grades and appearances. It was shown that among the cases of drug use, there were also the cases of misuse and abuse of drugs for the respondents or people around them. Reliability of pharmacists was shown to be high and many students were also satisfied with the pharmacists' guidance for medication. Conclusion: Currently many students are using different kinds of drug in daily life, and there is a possibility that the risk of misuse and abuse of drugs will be increased. Those age groups can easily engage in bad habit of drug use. Thus, promotion on accurate drug information has to be strengthened, and pharmacists are required to conduct correct guidance for drug user's medication in terms of use amount, usage, interactions among different drugs, and potential risks.

• Korean Journal of Clinical Pharmacy
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• v.28 no.2
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• pp.146-153
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• 2018

Objective: Multi-regional clinical trials have been widely used for accelerating global drug development by multinational pharmaceutical companies. In this study, we aimed to review and analyze the international trends in regulations and guidelines on multi-regional clinical trials by regulatory authorities and international organizations, such as International Conference on Harmonisation, for referring to policies, including development of domestic guidelines for multi-regional clinical trials. Methods: The policies, regulations, and guidelines published by the US Food and Drug Administration, European Medicines Agency, Pharmaceuticals and Medical Devices Agency (Japan), and China Food and Drug Administration were searched, and the International Conference on Harmonisation E17 draft guideline was reviewed. Results: The regulatory authorities in developed countries have developed and implemented regulations and guidelines on multi-regional clinical trials to promote simultaneous global drug development and evaluate the regional differences in drug safety and efficacy. International Conference on Harmonisation developed the draft guideline for planning/designing of multi-regional clinical trials in 2016, which recommends the general principles for strategy-related issues and design of multi-regional clinical trials, and for protocol-related issues, such as consideration of regional variability, subject selection, dose selection, endpoints, comparators, overall sample size, allocation to regions, collecting information on efficacy and safety, and statistical analysis. Conclusion: It is important to understand the international regulatory requirements for designing and planning of multi-regional clinical trials for global drug development. Moreover, it is necessary to prepare multi-regional clinical trial guidelines in accordance with the Korean regulation for clinical trials and drug administration.