• Journal of Digestive Cancer Reports
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• 제8권1호
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• pp.65-70
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• 2020

Although being one of the major causes of malignancy related death globally, hepatocellular carcinoma (HCC) has not received much attention in respect of novel drug development. Fortunately, several new drugs were found to be effective and tolerable in patients with advanced HCC from a number of phase 3 studies during the recent several years. Novel multi-targeted kinase inhibitors and immune checkpoint inhibitors were approved for clinical use, and combination strategies to maximize the potent of drugs demonstrated promising antitumor activity and safety with high response rate and improved safety profile. The increased number of available agents for HCC will contribute to change of treatment strategies and prognosis of patients with advanced HCC. Still, there is a many critical questions remain unanswered. Currently ongoing trials and future studies will provide better understanding of tumor biology and optimized criteria for patient selection and combination therapies.

• Journal of Pharmaceutical Investigation
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• 제6권3호
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• pp.58-69
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• 1976

It is well established that dissolution is freruently the rate limiting step in the gastrointestinal absorpton of a drug from a solid dosage from. The relationship between the dissolution rate and absorption is particularly distinct when considering drugs of low solubility. Consequently, numerous attempts have been made to modify the dissolution characteristics of poorly water soluble drugs. Since dissolution rate is directly proportional to surface area, one may increase the rate by decreasing the particle size of the drug. Levy has considered a number of methods by which a drug may be presented to the GI fludids in finely divided from. The direct method is the utilization of microcrystalline or micronized particles. A second method involves the administration of solutions from which, upon dilution with gastric fluids, the dissolved drug will precipitate in the form of very fine particles. A more unique way of obtaining microcrystalline dispersions of a drug has been ercently suggested by Sekiguchi et al. They have first proposed the formation of a eutectic mixture of a poorly water soruble drug with a physiologically inert, easily soluble carrier. When such systems are exposed to water or GI fluids, the soluble carrier will dissolve rapidly and the finely dispersed drug particles will then be released. It has been suggested by Shefter and Higuchi that the formation of crystalline solvate could be a powerful tool in affecting rapid disslution of highly insoluble substances. Goldberg et al. have noted that the formation of solid solution could reduce the particle size to a minimum and increase the dissolution rate as well as the solubility of the durgs. It has also been shown that the rates of solution of drugs were appreciably increased by coprectipitating the drug with soluble polymers. The increase was found to be sensitive to the method of preparation, the molecular weight of polymer and the particular ratio of drugs to polymer. Although several investigations have demontrated that the solubility and/or dissolution rates of drugs can be increased in this manner, little information is available in the literature related to the in vivo absorption pattern of drugs orally administered as PVP coprecipitates. Recently, however, it was demonstrated that both the rate and extent of absorption of the insoluble drug could be markedly enhanced when orally administered to rats in the form of a coprecipitate with PVP. The purpose of the present investigation was to ascertain the general appility of soluble polymer coprectation technique as a method for enhancing the in vitro dissolution rate of hydrophobic indomethacin. To accomplish this aim, the dissolution characteristics of pure indomethacin, indomethcin-polymer physical mixtures and indomethacin-polymer coprecipitates were quantitatively studied by comparing their relative dissolution rates. The solubility and dissolution behavior of these systems were also examined.

• 약학회지
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• 제58권4호
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• pp.262-267
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• 2014

Unused medication disposal is a burden due to the cost of disposing as well as the cost of the drugs. Investigating medication returns is expected to suggest areas of intervention to reduce unused medications. Purpose: The aim of this study was to examine types, quantity, costs, active pharmaceutical ingredients, and therapeutic category of the medications returned to community pharmacies. Method: From January 15, 2014 to February 28, 2014, the medications returned to the 17 community pharmacies in Gimhae, Jinju, and Incheon, Korea were examined. The pharmacists and student volunteers worked cooperatively to identify the medications and analyze drug cost of prescription pill medications returned to the pharmacies. Results: A total of 2,720 pills of prescription medication were analyzed and 91 active pharmaceutical ingredients were identified. According to the Anatomical Therapeutic Chemical (ATC) classification, the most predominant group was A (alimentary tract and metabolism) with 33.3%, followed by N (nervous system) with 15.0%. With regard to the drug cost of groups, group A was the highest with 26.6%, followed by J01 (antibacterials for systemic use) with 20.2% and N (nervous system) with 18.3%. The total cost of the oral pill prescription medications was 468,477 won. Conclusion: The result from this study implies that unused drugs impose a significant cost to the health care system in Korea. In this study, medicines used to treat gastrointestinal conditions were returned most frequently with the highest drug cost. Further research in nationwide level is necessary to establish strategies to reduce the wastage of unused medicines.

• 한국임상약학회지
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• 제16권2호
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• pp.155-164
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• 2006

Great inter-variability in drug response and adverse drug reactions is related to inter-variability of drug bioavailability, drug interaction and patient's disease and physyological state that cause change in absorption, distribution, metabolism and excretion of drugs. However, these alone do not sufficiently predict and explain inter-variability in drug response. In recent studies, it is reported that inter-variability in drug response and adverse drug reactions may largely resulted from genetically determined differences in drug absoption, distribution, metabolism and drug target proteins. Especially, the major human drug-metabolizing enzymes such as CYP450, N-acetyl tranferase, thiopurine S-methyl transferase, glutathione S-transferase are identified as the major gene variants that cause inter-individual variability in drug's response and adverse drug reactions. These variations may have most significant implications for those drugs that have narrow therapeutic index and serious adverse drug reactions. Therefore, the genetic variation such as polymorphisms in drug metabolizing enzymes can affect the response of individuals to drugs that are used in the treatment of depression, psychosis, cancer, cardiovascular disorders, ulcer and gastrointestinal disorders, pain and epilepsy, among others. This review describes the pharmacogenomics of the drug metabolizing enzymes associated with the drug response and its clinical applications.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.197-197
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• 1996

Helicobacter pylori (H. pylori) is a microaerophilic spiral bacterium and infection by it in the human stomach causes gastritis, furthermore, it is considered to be involved in the pathogenesis of peptic ulcers and the development of gastric carcinoma. We assessed the inhibitory activity of new antiulcer drugs against Helicobacter pylori. The activities of new antiulcer agents against Helicobacter pylori strains were determined by the standard agar dilution method with blood agar base #2, supplemented with 5% sheep blood and 4 antibiotics to support growth of these organisms. They were inoculated by multipoint inoculator and incubated at 37$^{\circ}C$ for 3 days under microaerophilic atmosphere. The MIC of antiulcer agents was the lowest concentration that inhibited visible growth of these organisms. According to results of various biochemical tests, these bacteria were identified as Helicobacter pylori strains. And the MIC results showed that the strains were very susceptible to omeprazole and YJA20379s. Some of YJA20379s were more potent than omeprazole. These results suggest that our new antiulcer drugs have potent inhibitory activity against Helicobacter pylori, so that our new antiulcer drugs might be useful for the clinical eradication of gastrointestinal Helicobacter pylori.

• 대한수의학회지
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• 제63권3호
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• pp.30.1-30.8
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• 2023

Metformin is a treatment used widely for non-insulin-dependent diabetes mellitus with few side effects and acts by inhibiting hepatic gluconeogenesis and glucose absorption from the gastrointestinal tract. Lymphoma is one of the most common hematological malignancies in dogs. Chemotherapy is used mainly on lymphoma, but further research on developing anticancer drugs for lymphoma is needed because of its severe side effects. This study examined the anticancer effects of metformin alone and in combination with 2-deoxy-D-glucose (2-DG), a glucose analog, on EL4 cells (mouse T cell lymphoma). Metformin reduced the metabolic activity of EL4 cells and showed an additive effect when combined with 2-DG. In addition, cell death was confirmed using a trypan blue exclusion test, Hochest 33342/propidium iodide (PI) staining, and Annexin V/PI staining. An analysis of the cell cycle and mitochondria membrane potential (MMP) to investigate the mechanism of action showed that metformin stopped the G2/M phase of EL4 cells, and metformin + 2-DG decreased MMP. Metformin exhibited anticancer effects as a G2/M phase arrest mechanism in EL4 cells and showed additive effects when combined with 2-DG via MMP reduction. Unlike cytotoxic chemotherapeutic anticancer drugs, metformin and 2-DG are related to cellular glucose metabolism and have little toxicity. Therefore, metformin and 2-DG can be an alternative to reduce the toxicity caused by chemotherapeutic anticancer drugs. Nevertheless, research is needed to verify the in vivo efficacy of metformin and 2-DG before they can be used in lymphoma treatments.

• 대한한방내과학회지
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• 제45권1호
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• pp.55-74
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• 2024

Objectives: This study reviewed the status of adverse event (AE) reporting in VigiAccess using anti-obesity agents as examples and explored the possibility of its use and future challenges. Methods: AE reports related to some representative drugs among herbal medicines (HMs), complex HM prescriptions, ingredients of supplements, and over-the-counter and prescription medicines were investigated using VigiAccess on February 1, 2024. Results: AE reports on prescription drugs were overwhelmingly higher than those on HMs or supplements. Although most reports were submitted from North America, reports on Ephedra sinica and green tea extract (GTE) were more from Asia and Europe, respectively. The female population reported more, and the difference in the sex ratio was the smallest for Ephedra spp. The age group was concentrated on young adults, but many older patients reported GLP-1 receptor agonist-related AEs. Symptoms related to the gastrointestinal and nervous systems were most commonly reported, but mental and cardiac disorders were common in Ephedra-type HMs. Hepatobiliary disorders are also commonly found in GTE-related reports. Conclusions: VigiAccess was useful for easily checking the global status of AE reporting for prescription drugs. However, several limitations were observed in using VigiAccess for HMs because of the few reports. Thus, it is necessary to increase the number of reports by education and to promote AE reporting among HM prescribers and users. The full range of HMs should be included in the pharmacovigilance system, and the coding and classification of HMs should be revised.

• 통합자연과학논문집
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• 제8권1호
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• pp.13-18
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• 2015

Cysteinyl leukotrienes are inflammatory mediators having important role in pathophysiological conditions such as asthma, allergic rhinitis and have been implicated in a number of inflammatory conditions including cardiovascular and gastrointestinal diseases. Most of the disease regulatory actions of the CysLTs are mediated through CysLT1 receptor. Hence in the present study, homology modeling of CysLT1 was performed because the availability of 3D structure would enhance the development of new drugs for inflammatory diseases. However the templates identified have low sequence identity which increases the complexity of modeling. Hence, homology modeling was performed using single template, multiple templates and also using threading I-TASSER server. The best model was selected based on the validation of the generated models using Ramachandran and ERRAT plot. The model developed could be useful for identifying crucial residues and docking study.

• Pediatric Infection and Vaccine
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• 제18권1호
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• pp.15-22
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• 2011

Invasive Candida infections (ICI) have become the third most common cause of late-onset infection among premature infants in the neonatal intensive care unit (NICU). Risk factors include birth weight less than 1,000 g, exposure to more than two antimicrobials, third generation cephalosporin exposure, parenteral nutrition including lipid emulsion, central venous catheter, and abdominal surgery. Candida colonization of the skin and gastrointestinal tract is an important first step in the pathogenesis of invasive disease. Strict infection control measures against the infection should be done in the NICU. The following practices are likely to contribute to reducing the rate of ICI: (1) restriction of broad-spectrum antibiotics, antacids and steroid; (2) introduction of early feeding and promoting breast milk. Fluconazole prophylaxis may be an effective control measure to prevent Candida colonization and infections in individual units with high incidence of fungal infection. In addition, there is a need of further data including the development of resistant strains and the effect on long-term neurodevelopmental outcomes of infants exposed to drugs before the initiation of routine application of antifungal prophylaxis in the NICU.

• Biomolecules & Therapeutics
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• 제10권2호
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• pp.89-98
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• 2002

In this study general pharmacological profiles of KI-60606 on the central nervous system, the cardiovascular system and the other organs were investigated. The dosages given were 0,5, 10 and 25 mg/kg and drugs were administered intravenously. The animals used for this study were mice, rats, cats and guinea pigs. KI-60606 showed no effects on general behavior, motor coordination, spontaneous locomotor activity, hexobarbital-induced hypnosis time, body temperature, analgesic activity, anticonvulsant activity and contraction of nictitating membrane in cats. Furthermore KI-60606 showed no effects on blood pressure, heart rate, LVP (left ventricular peak systolic pressure), LVEDP (left ventricular end diastolic pressure), LVDP (left ventricular developing pressure), DP(double product), CFR(coronary flow rate), smooth muscle contraction using guinea pig ileum and gastric secretion at all dosage tested except the increase of gastrointestinal transport and urinary $K^+$ excretion.