• Korean Journal of Clinical Pharmacy
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• v.26 no.2
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• pp.121-127
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• 2016

Objective: Until now, there is minimal number of research for overall domestic status of orphan drug use in Korea. The purpose of this study is to identify the list of orphan drugs available in Korea and to understand the status of orphan drug usage in tertiary Hospitals and rare incurable disease Hospital. Methods: We made domestic orphan drug lists based on available orphan drugs in Korea. Based on this lists, we conducted e-mail survey from August, 2014 to September, 2014 to identify domestic status of orphan drug usage including the availability and management of orphan drugs. Results: There are three hundred and eighteen orphan drugs (184 ingredients) registered in Ministry of Food and Drug Safety. Among the three hundred and eighteen orphan drugs, Two hundred and twenty-eight drugs (102 ingredients) were selected. Information on each item was collected and documented with generic and brand names, manufacturers, wholesalers, indications, FDA approval status and insurance coverage. Forty-three tertiary hospitals and thirty-two rare incurable hospitals responded to the survey questionnaire (57.3%). According to the survey result, the antineoplastics and immunomodulating agents group has the highest percentage (40%) usage in the hospital. Of fortythree tertiary hospitals, thirteen hospitals manage orphan drugs separately (30.2%). Based on the reply, most of the healthcare professionals commented the drug information related to efficacy and safety including medication counseling of orphan drugs is insufficient. Conclusion: Through this study we anticipate providing an understanding of orphan drug usage status in Korea. We found the limited resources to the information on orphan drugs and this information requires updating on a regular basis. This can be the basis for further studies about preparing drug information, educational resources for rare disease patients.

• Korean Journal of Clinical Pharmacy
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• v.28 no.4
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• pp.333-341
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• 2018

Objective: Tumor necrosis factor-alpha (TNF-alpha) inhibitors are used as a treatment in various immune-mediated inflammatory diseases (IMIDs). Tuberculosis (TB) risk is reported in several meta-analyses in patients treated with TNF-alpha inhibitors. The purpose of this study is to collect, review, and evaluate the TB risk in TNF-alpha inhibitors according to IMIDs indications and between soluble-receptor TNF-alpha inhibitor and monoclonal-antibody TNF-alpha inhibitors. Methods: A systematic literature search on systematic reviews and meta-analyses was performed in PubMed, MEDLINE, Cochrane library, and EMBASE. We identified meta-analyses that evaluated TB infection risk of TNF-alpha inhibitors in IMIDs patients. Results: Thirteen meta-analyses including 41 study results were included in this umbrella review. IMIDs patients treated with TNF-alpha inhibitors had an increased risk of TB than control group (placebo with or without standard therapy patients) (relative risk ratio (RR) 2.057, 95% confidence interval (CI) 1.697 to 2.495). Among them, RA patients with TNF-alpha inhibitors had a higher risk of TB than control group (RR 1.847, 95% CI 1.385 to 2.464), and non-RA patients with TNF-alpha inhibitors had an increased risk of TB (RR 2.236, 95% CI 1.284 to 3.894). In subgroup analysis on TB risk between soluble-receptor TNF-alpha inhibitor and monoclonal-antibody TNF-alpha inhibitors in RA patients, the analysis indicated that monoclonal-antibody TNF-alpha inhibitors had higher risk of TB than soluble-receptor TNF-alpha inhibitor (RR 2.880, 95% CI 1.730 to 4.792). Conclusion: This umbrella review confirms that the risk of TB is significantly increased in TNF-alpha inhibitor treated patients compared to control group.

• Biomolecules & Therapeutics
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• v.32 no.3
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• pp.379-389
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• 2024

This study was aimed to evaluate endogenous metabolic changes before and after cisplatin and radiation therapy in patients with cervical cancer via untargeted metabolomic analysis using plasma samples. A total of 13 cervical cancer patients were enrolled in this study. Plasma samples were collected from each patient on two occasions: approximately one week before therapy (P1) and after completion of cisplatin and radiation therapy (P2). Of the 13 patients, 12 patients received both cisplatin and radiation therapy, whereas one patient received radiation therapy alone. The samples were analyzed using the Ultimate 3000 coupled with Q Exactive^TM Focus Hybrid Quadrupole-Orbitrap^TM mass spectrometry (Thermo Fisher Scientific, Waltham, MA, USA). Chromatographic separation utilized a Kinetex C18 column 2.1×100 mm (2.6 ㎛) (Phenomenex, Torrance, CA, USA), and the temperature was maintained at 40℃. Following P2, there were statistically significant increases in the concentrations of indoxyl sulfate, phenylacetylglutamine, Lysophosphatidyethanolamine (LysoPE) (18:1), and indole-3-acetic acid compared with the concentrations observed at P1. Specifically, in the human papillomavirus (HPV) noninfection group, indoxyl sulfate, LysoPE (18:1), and phenylacetylglutamine showed statistically significant increases at P2 compared with P1. No significant changes in metabolite concentrations were observed in the HPV infection group. Indoxyl sulfate, LysoPE (18:1), phenylacetylglutamine, and indole-3-acetic acid were significantly increased following cisplatin and radiation therapy.

• Korean Journal of Clinical Pharmacy
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• v.28 no.4
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• pp.342-346
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• 2018

Background: Green tea extracts are approved as nonprescription drug and available as health functional foods, health foods, and beverages. Clinical information on the products is lacking. Methods: Information about the products on green tea nonprescription drugs was obtained from the website of the Korea Pharmaceutical Information Center. The Naver, i.e., a top ranking online search portal, was used for compiling the list of the health functional food products using key words of 'green tea catechin' on August 23, 2018. The recommended daily dosages of catechins were calculated as 30% of the total dried mass of green tea and about 50% of the catechins were considered as epigallocatechin gallate (EGCG). Results: A total of two types of nonprescription drugs containing green tea powder or extracts, nine health functional food products, and three types of health foods were found. The regulatory requirements of the EGCG exceeding 800 mg were reported to be associated with adverse effects of elevated liver enzyme. If consumers take several green tea products concurrently, such as nonprescription drugs with health functional foods or health foods, it could exceed the recommended amount of EGCG. Conclusion: The concurrent use of green tea products as nonprescription drugs, health functional foods, and healthy foods may lead to an increased exposure to EGCG. Pharmacists should be aware the availability of various types of green tea products and the potential risk of liver toxicity due to excessive consumption of EGCG.

• Archives of Pharmacal Research
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• v.21 no.6
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• pp.753-758
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• 1998

Sixteen novel 2-substituted acetyl amino-5-alkyl-1,3,4-thiadiazol were synthesized and screened for their pharmacological activities. A few of the compounds namely 11, 12 and 16 showed anti-inflammatory activities comparable to phenylbutazone. Compound 12 also showed significan non-specific spasmolytic activity. Diuretic activity of compound 15 at a dose level of 90mg/kg p.o. was two fold higher compared to 50mg/kg p.o. of furosemide. Comparable diuresis was aso produced by compounds 9, 10, and 16.

• Journal of Pharmaceutical Investigation
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• v.30 no.2
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• pp.139-143
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• 2000

Gene therapy is becoming a very promising and feasible medical intervention as the understanding of human diseases extends to their molecular levels. Since the first US Food and Drug Administration (FDA)-approved human gene therapy protocol was approved in 1990, over 300 human clinical trial protocols had been approved worldwide so far. Even though some of the domestic gene therapy clinical trials also proved promising and more are awaiting, it should be emphasized that many safety aspects as well as effectiveness aspects should be considered during the development process. Moreover, there seems to be less restricted guidelines from the National Control Authority (NCA) in initiating human clinical trials. This article is intended to suggest some basis and points to consider in the development and evaluation of gene therapy products including antisense oligonucleotides pharmaceuticals.

• Korean Journal of Clinical Pharmacy
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• v.23 no.3
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• pp.232-238
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• 2013

Background: Although thromboembolism is common and one of the major causes of mortality in cancer patients, maintaining therapeutic anticoagulation effect with warfarin is challenging. This study aimed to determine the prevalence and the causes of non-therapeutic INR (International Normalized Ratio) in cancer patients. Methods: Medical and pharmacy records for cancer patients managed by the pharmacist-run anticoagulation service (ACS) between May, 2010 and April, 2011 at Seoul National University Hospital were retrospectively reviewed. The causes of non-therapeutic INR were identified and compared with the results from a former study with mechanical heart valve patients. Results: A total of 335 cancer patients and 6,737 patient-visits were analyzed producing 68% (n=4,590) of non-therapeutic INR readings. Eighty-five percent of the non-therapeutic INR readings were categorized as sub-therapeutic. Frequent causes linked to non-therapeutic INR included inadequate dosage adjustment (21.8%), changes in health status (11.8%), dietary changes (8.1%), and drug interactions (4.2%). More than half of the non-therapeutic INR values had no known etiology. As causes for non-therapeutic INR, changes in health status (p<0.0001), adverse reactions (p<0.0001), and dietary changes (p=0.017) were statistically more frequent in cancer patients than in patients with mechanical heart valves. Furthermore, exposure to sub-therapeutic INR were more prevalent in cancer patients than in patients with mechanical heart valve (p<0.0001). Conclusions: This study shows that there is a tendency to keep the level of INR low and that health status change, dietary change, and drug interactions are found to be frequent causes for non-therapeutic INR in cancer patients.

• Environmental Analysis Health and Toxicology
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• v.31
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• pp.16.1-16.9
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• 2016

Objectives Banha-sasim-tang (BST), which consists of seven different herbs, is one of the most popular herbal formulae for treating gastrointestinal disorders in Eastern Asia. The commonly used herbal medicine is often co-administered with other therapeutic drugs, which raises the possibility of herb-drug interactions and may modify the clinical safety profile of therapeutic drugs. Methods We investigated the potential herb-drug interactions between BST extract and midazolam (MDZ) in mice. The area under the plasma concentration-time curve (AUC) of MDZ and 1'-hydroxymidazolam (1'-OH-MDZ) was evaluated for both oral and intraperitoneal administration of MDZ, following oral administration of BST (0.5 and 1 g/kg). Results It was found that the AUC of MDZ and 1'-OH-MDZ was lower in case of oral administration of MDZ. Administration of BST extract was not associated with hepatic cytochrome P450 activity. BST extract induced a strong reduction in pH and it has been reported that oral mucosal absorption of MDZ is lower at low pH. The decreased absorption rate of MDZ might be caused by the ingredients of BST and may not be related to other factors such as increased excretion of MDZ by P-glycoprotein. Conclusions The altered pharmacokinetics of midazolam caused by co-administration with BST in vivo could be attributed to a decrease in pH and subsequent reduction of MDZ absorption rate.

• International Journal of Industrial Entomology and Biomaterials
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• v.35 no.1
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• pp.14-21
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• 2017

Gastric ulcer is a clinical symptom characterized by inflammation of the gastric mucosa. Stress and alcohol consumption have been identified as the major cause of gastric ulcer. However, the effects of silkworms on ethanol-induced gastric ulcer have not been studied yet. The mature silkworms that are difficult to eat have become easier to ingest due to recent technological development to make steaming and freeze-drying mature silkworm larval powder (SMSP). In this study, we investigated whether three silkworm varieties, Baekokjam, Golden-silk and Yeonnokjam could alleviate ethanol-induced gastric mucosal damage in vivo. Sprague-Dawley rats pretreated with 3 SMSPs (0.1 or 1 g/kg BW) or normal diet (AIN-76A) were exposed to absolute ethanol (3 g/kg BW, 3 h) by oral gavage. Morphological examination included ulcer index as a measurement of hemorrhages and hematoxylin and eosin staining was performed to analyze the severity of gastric ulcer. Results of macroscopic examination suggested that all 3 SMSPs pretreatment significantly protected gastric mucosa against ethanol-induced damage. Microscopic observations demonstrated significant mucosal erosion and inflammation in ethanol-treated rats, which was abrogated in rats pretreated with 3 SMSPs. In addition, pretreatment with all 3 SMSPs showed significant decreases the expression of pro-inflammatory mediators, IL-6 and cyclooxygenase-2. Among SMSP from 3 varieties of silkworm, preadministration of 1 g/kg Baekokjam SMSP showed the most effective protective effect against ethanol-induced gastric ulcer. These results suggest that Baekokjam SMSP can be a potential gastroprotective agent against ethanol-induced gastric ulcer.

• Korean Journal of Clinical Pharmacy
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• v.22 no.1
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• pp.65-72
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• 2012

Antidepressants are frequently prescribed for a wide range of symptoms. Surveys in several countries have suggested that negative attitudes towards antidepressants are common. However, there has been limited research associated with the attitudes in Korea. Therefore, this quantitative descriptive study describing the perception and attitudes toward antidepressants was performed using healthy people and outpatients who are not taking antidepressants. The surveys by means of self-reporting questionnaires showed negative attitudes towards antidepressants (74.2%). But, 74.2% of above participants gave positive answers to take antidepressants when they are counseled by medical professionals. Higher rates of negative attitudes were found in younger age group ("it causes addiction") and healthy volunteers and urban area groups ("it causes physical harm"). Study participants without experiences in taking antidepressants showed more negative attitudes although the difference was not statistically significant. Based on the results, accurate and objective information about antidepressants needs to be provided by well-trained health professionals.