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A recent in vitro cardiovascular safety pharmacology test uses cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) to overcome the limitations of the classical test systems, such as species differences and local channel analysis. The Comprehensive in vitro Proarrhythmia Assay (CiPA) is a new proarrhythmia screening paradigm proposed by a CiPA steering expert group, which essentially requires iPSCs derived cardiomyocyte-based electrophysiological evaluation technology. Moreover, the measurement of the contractile force is also emerging as an important parameter to recapitulate non-proarrhythmic cardiotoxicity. Therefore, we constructed an multielectrode assay (MEA) evaluation method that can measure the electrophysiological changes with 6 reference drugs in hiPSC-derived cardiomyocytes. Subsequently, it was confirmed that the electrophysiological were changed in accordance with the mechanism of action of the drugs. Furthermore, based on the multi-probe impedance, we confirmed the decrease in contractile force due to treatment with drugs, and developed a platform to evaluate cardiotoxicity according to drugs along with field potential changes. Our excitation–contraction coupling cardiotoxicity assessment is considered to be more supportive in cardiac safety studies on pharmacologic sensitivity by complementing each assessment parameter.

The paper deals with the selection of 3D display devices in accordance with the user`s conveniences and accuracy of spatial information by applying 3D display devices to Spatial Information Update System (SIUS) which generate edit and update digital thematic maps. After applying different manufacturer`s 3D display devices to SIUS, aerial images acquired from the stereo images were displayed through the devices and spatial information was extracted from the displayed 3D images. Assessment of 3D display devices were based on quantitative and qualitative analysis on accuracy of spatial information and user`s conveniences. Planar`s PL2020 and Redrover`s Tru3Di 3D monitor has expressed outstanding display environment in 3D related tasks for the generation of spatial information compared to other 3D display devices. System improvement is expected regarding accuracy of spatial information, work efficiency and user`s conveniences.

Toxicogenomics has the potential to be used for the regulatory decision making to predict toxicity in developing new drugs. We have identified the classifiers for hepatotoxicity prediction in nonsteroidal anti inflammatory drugs (NSAIDs) through analyzing differential gene expression profiles of hepatotoxic and nonhepatotoxic compounds using HepG2 cell. 100 μM of 8 hepatotoxic and 8 nonhepatotoxic NSAIDs were treated to HepG2 cell and the analysis of gene expression changes after 24 h allowed a set of genes to be identified differentiating hepatotoxicants from nonhepatotoxicants by statistical method. The hepatotoxicity prediction model was built using the selected 77 genes. These genes and pathways, commonly regulated by hepatotoxicants, may be indicative of the early characterization of hepatotoxicity and possibly predictive of later hepatotoxicity onset. 4 test compounds including hepatotoxic and nonhepatotoxic NSAIDs were used for validating the prediction model and the accuracy was 100%. Given that the specificity and sensitivity showed 100%, these are the most precise classifiers identified until now.

To examine the effects of food on plasma concentration and bioavailability of fenofibrate administered as a sustained-release capsule.Twenty-four healthy Korean volunteers were enrolled in a randomised, open-label, balanced, three-treatment, three-period, three-sequence, single oral dose, crossover pharmacokinetic study. A single dose of fenofibrate (250 mg sustained-release capsule) was administered on three occasions -- after overnight fasting, after consumption of a standard breakfast and after a high-fat breakfast. Serial blood samples were collected for the next 72 hours. Plasma fenofibric acid concentrations were measured by high-performance liquid chromatography, and pharmacokinetic parameters were calculated.The pharmacokinetic parameters were significantly affected by food intake. The high-fat breakfast affected the rate of absorption of fenofibrate more than the standard breakfast and fasted conditions. Specifically, the area under the plasma concentration-time curve from time zero to infinity (AUC(infinity)) and peak plasma concentration (C(max)) increased 2.45-fold and 2.89-fold, respectively, between the fasted and standard-fed conditions (p0.01). In addition, the high-fat meal caused 3.34-fold and 3.82-fold increases compared with the fasted condition in AUC(infinity) and C(max), respectively. A one-compartment open model with lag time successfully described the plasma concentrations of fenofibric acid.In healthy volunteers, AUC(infinity) and C(max) of fenofibrate, when administered via sustained-release capsules immediately after the consumption of food, was increased significantly from the fasting conditions (p0.01). The greatest AUC(infinity) and C(max) occurred when the capsules were taken after a high-fat breakfast.

In Korea, generic drug and bioequivalence test are the hot issues since a new medical system of separation of dispensary from medical practice was started in 2000. The KFDA(Korea FDA) had revised several times . In vitro dissolution test has been extensively used as a quality control tool for solid oral dosage forms. In an effort to minimize unnecessary human testing, in vitro/in vivo correlations (IVIVC) between in vitro dissolution and in vivo bioavailability are increasingly becoming an integral part on extended release drug product development. The recently published US guidance, will be helpful for us to make our own guideline.

After new medical system of separation of dispensary from medical practice was started in 2000 in Korea, to expand bioequivalence-proven drug products and to ensure the credibility of the therapeutic equivalence of generic drugs are hot issues in Korea. It will be obligatory to submit bioequivalence reports for getting licenses of all generic prescription drugs in the near future. Like other countries such as US and Japan, the KFDA also has a plan to re-evaluate the already approved drugs by bioequivalence studies. Therefore, it becomes more necessary to develop bioequivalence-demonstrating methods for specific preparations such as topical drug products among already approved drug products. There are some differences between US and Japanese guidances of bioequivalence studies of generic drug products for topical use. The information on Japanese guidance and the guidance's Q&As is already provided in our previous paper. In this paper, we examined the US guideline published in 1995 and compared with the Japanese guideline, which will give a useful information to make a guidance on bioequivalence studies of topical drug products in Korea.

A new medical system of separation of dispensary from medical practice was started in 2000 in Korea. To expand bioequivalence-proven drug products and to ensure the credibility of the therapeutic equivalence of generic drug are hot issues in Korea. The KFDA also has a plan to revise the pharmaceutical affairs law that bioequivalence reports of all the generic prescription drugs should be submitted to the KFDA in the application for drug approval. Therefore, it becomes more necessary to develop bioequivalence-demonstrating methods for specific preparations such as topical drug products. There are some differences between US and Japanese guidances of bioequivalence studies of generic drug products for topical use. In this paper, we examined the recently published Japanese guideline, Guideline for Bioequivalence Studies of Generic Products For Topical Uses, and Q&A of the guideline, which will be references to make a guidance on bioequivalence studies of topical drug products in Korea.

A new medical system was started in Korea in 2000 and pharmaceutical affairs law was revised in 2001. According to the revised law, generic substitution is permitted only to the drug products which are proven to be bioequivalent to the reference listed drugs. To expand the list of bioequivalence-proven drug products and to ensure the credibility of the therapeutic equivalence of generic drug are the hot issues in Korea. Also, the KFDA has a plan to revise the pharmaceutical affairs law that bioequivalence reports of all the generic prescription drug products should be submitted to the KFDA for drug approval after July in 2004. Therefore, it is increasing the necessity to develop the bioequivalence-demonstrating methods for specific drug substances and preparations which require to conduct food-effect bioavailability or bioequivalence study. There are some differences between US and Japanese guidances of food-effect bioavailability and bioequivalence studies. In this paper, we examined the recently published US guidance about food-effect study and it will be a reference to make our own guidance about food-effect bioavailability and bioequivalence guidances in Korea.