• YAKHAK HOEJI
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• v.26 no.4
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• pp.223-229
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• 1982

Uremia is associated with defective protein binding of weakly acidic drugs, whereas the protein binding of basic drugs tends to be normal. The exact chemical nature of compound(s) and mechanism for these changes as yet is unknown, and has not been defined. Organic solvent extraction of pooled normal human urine following hydrolysis by hydrochloric acid produced an extract, which when added to normal human serum, was capable of inducing binding defects similar to those in uremia. Binding defects were observed with the weakly acidic drugs such as nafcillin, salicylate, sulfamethoxazole and phenytoin while the binding of the basic drugs such as trimethoprim and quinidine were unaffected. The binding defects induced by the hydrolyzed urine extract could readily be corrected by same organic solvent extraction of acidified serum and the defects could be transferred to the normal human serum using the organic solvent layer at the physiologic pH (7.4). Followed by reacidification ind extraction of the binding defects induced serum with the same solvent, separated several fractions were obtained on thin-layer chromatography. One of these fractions could reinduce the binding defects and this factor(s) is apparently weakly acidic compounds and tightly bound to serum at physiologic pH, but extractable at acidic pH, and its molecular weight range is approximately 500 or less similar to those seen in uremia. These findings strongly support the hypothesis that the drug binding defect in uremia is due to the accumulation of endogenous metabolic products which arc normally excreted by the kidneys but accumulate in renal failure.

• Archives of Pharmacal Research
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• v.25 no.4
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• pp.397-415
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• 2002

This paper deals with a crucial mechanism for interaction of basic drugs and cardiac glycosides at the hepatic uptake level. Available literature data is provided and new material is presented to picture the differential transport inhibition of bulky (type2) cationic drugs by a number of cardiac glycosides in rat liver. It is shown that the so called organic anion transporting peptide 2 (oatp2) is the likely interaction site: differential inhibition patterns as observed in oocytes expressing oatp2, could be clearly identified also in isolated rat hepatocytes, isolated perfused rat liver and the rat in vivo. The anticipation of transport interactions at the hepatic clearance level should be based on data on the relative affinities of interacting substrates for the transport systems involved along with knowledge on the pharmacokinetics of these agents as well as the chosen dose regimen in the studied species. This review highlights the importance of multispecific tranporter systems such as OATP, accommodating a broad spectrum of organic compounds of various charge, implying potential transport interactions that can affect body distribution and organ clearance.

• YAKHAK HOEJI
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• v.55 no.5
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• pp.426-431
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• 2011

This study was performed to investigate the current regulatory guidances of safety and efficacy evaluation for the development and approval of stereoisomeric drugs in US, EU, Canada and Japan. The important categories for the development of stereoisomeric drugs are classified as 1) development of a single enantiomer as a new active substance 2) development of a racemate as a new active substance 3) development of a new single enantiomer from an approved racemate. The regulatory documents adopted in major countries for the safety and efficacy evaluation of stereoisomeric drugs were investigated with the focus on three major categories mentioned above. For the regulatory approval of stereoisomeric drugs in Korea, it is expected that the investigated results obtained in this study will be useful for the basic materials to ensure the safety and efficacy of stereoisomeric drugs as well as the stereochemical issues in chiral drug development in domestic pharmaceutical company.

• BMB Reports
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• v.51 no.4
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• pp.167-173
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• 2018

Experimental results obtained from research using only one sex are sometimes extrapolated to both sexes without thorough justification. However, this might cause enormous economic loss and unintended fatalities. Between years 1997 and 2000, the US Food and Drug Administration suspended ten prescription drugs producing severe adverse effects on the market. Eight of the ten drugs caused greater health risks in women. Serious male biases in basic, preclinical, and clinical research were the main reason for the problem. This mini-review will describe why and how funding organizations such as the European Commission, the Canadian Institutes of Health Research, and the US National Institutes of Health have tried to influence researchers to integrate sex/gender not only in clinical research, but also in basic and preclinical research. Editorial policies of prominent journals for sex-specific reporting will also be introduced, and some considerations in integrating sex as a biological variable will be pointed out. To produce precise and reproducible results applicable for both men and women, sex should be considered as an important biological variable from basic and preclinical research.

• Journal of Ginseng Research
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• v.45 no.1
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• pp.22-31
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• 2021

Atherosclerosis (AS) is a leading cause of cardiovascular diseases (CVDs) and it results in a high rate of death worldwide, with an increased prevalence with age despite advances in lifestyle management and drug therapy. Atherosclerosis is a chronic progressive inflammatory process, and it mainly presents with lipid accumulation, foam cell proliferation, inflammatory response, atherosclerotic plaque formation and rupture, thrombosis, and vascular calcification. Therefore, there is a great need for reliable therapeutic drugs or remedies to cure or alleviate atherosclerosis and reduce the societal burden. Ginsenosides are natural steroid glycosides and triterpene saponins obtained mainly from the plant ginseng. Several recent studies have reported that ginsenosides have a variety of pharmacological activities against several diseases including inflammation, cancer and cardiovascular diseases. This review focuses on describing the different pharmacological functions and underlying mechanisms of various active ginsenosides (Rb1,-Rd, -F, -Rg1, -Rg2, and -Rg3, and compound K) for atherosclerosis, which could provide useful insights for developing novel and effective anti-cardiovascular drugs.

• Journal of Microbiology and Biotechnology
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• v.30 no.12
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• pp.1843-1853
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• 2020

COVID-19, caused by the novel coronavirus SARS-CoV-2, has spread globally and caused serious social and economic problems. The WHO has declared this outbreak a pandemic. Currently, there are no approved vaccines or antiviral drugs that prevent SARS-CoV-2 infection. Drugs already approved for clinical use would be ideal candidates for rapid development as COVID-19 treatments. In this work, we screened 1,473 FDA-approved drugs to identify inhibitors of SARS-CoV-2 infection using cell-based assays. The antiviral activity of each compound was measured based on the immunofluorescent staining of infected cells using anti-dsRNA antibody. Twenty-nine drugs among those tested showed antiviral activity against SARS-CoV-2. We report this new list of inhibitors to quickly provide basic information for consideration in developing potential therapies.

• Journal of Integrative Natural Science
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• v.9 no.4
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• pp.228-233
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• 2016

Cysteinyl leukotrienes are inflammatory mediators having important role in pathophysiological conditions such as asthma and allergic rhinitis. CysLT1 receptor mediates most of the disease regulatory actions of the CysLTs and it is been implicated in a number of inflammatory conditions including gastrointestinal and cardiovascular diseases. Hence in the present study, molecular docking of CysLT1 was performed with its potent and orally efficacious antagonist CP-199330 and CP-199331. The aim of this study was to compare the interaction of CP-199330 and CP-199331 with known drugs such as Zafirlukast, Pranlukast and Montelukast which had already showed clinical efficacy in the treatment of asthma. The residues such as TYR83, GLN274, LYS311 and SER313 were found to interact with both the antagonist and the known drugs. Also, we noticed the docking scores and interaction of the antagonists were comparable with the known drugs. Hence these antagonists could serve as better drugs for the treatment of allergy.

• Biomolecules & Therapeutics
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• v.26 no.4
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• pp.343-349
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• 2018

Although drugs such as barbiturates and benzodiazepines are often used for the treatment of insomnia, they are associated with various side effects such as habituations, tolerance and addiction. Alternatively, natural products with minimal unwanted effects have been preferred for the treatment of acute and/or mild insomnia, with additional benefits of overall health-promotion. Basic and clinical researches on the mechanisms of action of natural products have been carried out so far in insomnia treatments. Recent studies have been focusing on diverse chemical components available in natural products, with an interest of developing drugs that can improve sleep duration and quality. In the last 15 years, our co-workers have been actively looking for candidate substances from natural products that can relieve insomnia. This review is, therefore, intended to bring pharmacological data regarding to the effects of natural products on sleep duration and quality, mainly through the activation of $GABA_A$ receptors. It is imperative that phytochemicals will provide useful information during electroencephalography (EEG) analysis and serve as an alternative medications for insomnia patients who are reluctant to use conventional drugs.

• Archives of Pharmacal Research
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• v.10 no.4
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• pp.245-249
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• 1987

Cardiovascular disease is at present the leading cause of deth in the United States and other in dustrilized countries. A major contributing factor of cardiovascular disease is essential hypertension. Untreated, essential hypertension is considered a risk factor for sudden death due to myocardial infarctions, as well as a risk factor for cerebral vascular disease, renal failure and congestive heart failure. During the last decade, significant progress has been made in the basic knowledge of the pathogenesis of hypertension as well as in the development of new antihypertensive drugs.

• Korean Journal of Clinical Pharmacy
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• v.23 no.2
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• pp.97-105
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• 2013

Background: This study was aimed to establish the systematic management methods of tar color additives used in Korea for drugs and quasi-drugs. Although tar color additives have been used in various areas, safety problems are continuously being reported by several studies. For that reason, major countries like US, Japan, Europe are trying to update the safety information of tar color additives and the related management methods, and Korea also need to complement them based on the updated information for their safer use. Method: This report includes the compared information of all legally used tar color additives of each country, such as color additive name, compound name and chemical abstracts service registry number. Conclusion: It is expected that these investigated results will be useful as the basic materials for proper management guidelines of tar color additives in Korea.