• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6829-6835
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• 2014

Chemotherapy is the primary therapy for malignant lymphoma (ML). However, the clinical outcome is still far from satisfactory. Consequently, an understanding of the mechanism of modulating cancer cell invasion, migration and metastasis is important for the development of more effective chemotherapeutic agents. FNC, 2'-deoxy-2'-${\beta}$-fluoro-4'-azidocytidine, a novel cytidine analogue, has demonstrated significantly inhibitory effects on proliferation of several non-Hodgkin lymphoma (NHL) cell lines. A previous study indicated that FNC effectively inhibited the growth of Raji and JeKo-1 cells in dose-time dependent effects with $IC_{50}$ values of $0.2{\mu}M$ and $0.097{\mu}M$, respectively. This study was focused on investigating the anti-invasive properties of FNC on NHL cells and its potential mechanisms of action. Cell adhesion and transwell chamber assays were utilized to investigate the anti-invasive effects of FNC on Raji and JeKo-1 cells. Real-time PCR and Western blotting were employed to qualify the expression of ${\beta}$-catenin, the glycogen synthase kinase-3 beta (GSK-$3{\beta}$), E-cadherin vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The results revealed that FNC remarkably inhibited the adhesion, migration and invasion of two human aggressive non-Hodgkin lymphoma cell lines in a dose dependent manner. Furthermore, ${\beta}$-catenin, MMP-2, MMP-9, VEGF mRNA and protein levels were decreased after FNC treatment, while GSK-$3{\beta}$ and E-cadherin increased. Our studies thus provide evidence and a rationale that FNC may offer an effective chemotherapeutic agent by regulating the invasion and metastasis of aggressive non-Hodgkin lymphoma via inhibition of the Wnt/${\beta}$-catenin signaling pathway.

• Korean Journal of Clinical Pharmacy
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• v.19 no.2
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• pp.146-152
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• 2009

Purpose : 본 연구의 목적은 항암치료로 인한 빈혈환자의 치료에서 epoetin alpha (rHuEPO) 피하주사 시, 주일회 요법과 주삼회요법의 헤모글로빈(hemoglobin, Hb) 상승 효과를 비교하는 것이다. Methods : 본 연구는 1999년 3월부터 2005년 3월까지 국립암센터에서 항암치료로 인한 빈혈로 epoetin alpha를 투여 받은 환자를 대상으로 의무기록의 자료를 후향적으로 수집하여 분석하였다. 연구에 포함된 환자는 rHuEPO 10,000 IU 주삼회투여군(n = 127)과 20,000 IU 주일회투여군(n = 81)으로 구분되었으며, 이들은 필요에 따라 경구용 철분보조제를 섭취하였다. Epoetin alpha 치료 시작 후 최대 8주까지 2주 간격으로 Hb 수치변화를 분석하였다. Results : 치료 시작 시점의 rHuEPO 10,000 IU 주삼회투여군과 20,000 IU 주일회투여군의 평균 Hb수치는 유사하였 다 (9.4 g/dL vs. 9.7 g/dL). Epoetin alpha 치료 후 8주까지 두 그룹간의 헤모글로빈 수치의 상승 정도에는 유의한 차이가 없었다 ($1.57{\pm}1.39$ g/dL vs. $1.68{\pm}1.35$ g/dL, p=0.59). 또한 경구용 철분보조제 투여여부, cisplatin 포함 항암제 투여여부 및 성별에 따른 군의 분류에 있어서도 rHuEPO 10,000 IU 주삼회투여군과 20,000 IU 주일회투여군의 평균 Hb 상승수치는 유의한 차이를 보이지 않았다. Conclusion : 한국인에서 항암치료로 인한 빈혈의 치료 시에 rHuEPO 20,000 IU 주일회투여 용법은 10,000 IU 주 삼회투여 용법과 유사한 Hb 상승효과를 가진다.

• Korean Journal of Clinical Pharmacy
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• v.27 no.3
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• pp.178-185
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• 2017

Objective: Because of communication difficulties, the hearing-impaired face many disadvantages throughout their lives. One of those is limited access to health care services, particularly medication service. Though they suffer from problems related to taking medication properly, there have been few studies on their actual condition of medication use in Korea. This study is to investigate any obstacles to properly taking medications and, therefore, to suggest preliminary evidence for policy measures to improve safe medication use among the hearing-impaired. Methods: Study participants consisted of hearing-impaired individuals living in Seoul. We also interviewed two sign language interpreters in order to illuminate health care state of the hearing-impaired. In-depth interview for each study participant was recorded and was translated into a written script for analysis. Results: Study participants were comprised of four women (66.6%) and two men (33.3%). There were one participants in 20's, two participants in 30's, one 40's, and two 50's. Sign language interpreters were all women. One was in her 30's and the other was in her 40's. Communication difficulties have been found to be key barrier to use medication safely. A negative image of pharmacists also hinders safe medication usage, lowering access to local pharmacy and leading discretional self-medication. This article provides pharmacists with solutions to promote adherence in this population. Conclusion: The hearing-impaired had limited access to medication-related information as well as using services in a hospital and local pharmacy due to their disability. Institutional improvement for safe medication usage among the hearing-impaired is necessary.

• Korean Journal of Clinical Pharmacy
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• v.28 no.1
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• pp.24-29
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• 2018

Background: Cyclosporine is an immunosuppressive agent used to treat and prevent graft versus host reaction (GVHR)-a complication associated with stem cell transplantation. This study aimed to develop a population pharmacokinetic model of cyclosporine and investigate factors affecting cyclosporine clearance in pediatric hematopoietic stem cell transplant patients. Methods: A total of 650 cyclosporine concentrations recorded in 65 patients who underwent hematopoietic stem cell transplantation were used. Data including age, sex, weight, height, body surface area (BSA), type of disease, chemotherapy before stem cell transplantation, type of donor, serum creatinine levels, total bilirubin concentration, hematocrit value, and type of concomitant anti-fungal agents and methylprednisolone used were retrospectively collected. Data related to cyclosporine dosage, administration time, and blood concentration were also collected. All data were analyzed using the non-linear mixed effect model; a two-compartment model with first-order elimination was used. Results: The population pharmacokinetic model of cyclosporine using the NONMEM program was as follows: $CL(L/h)=5.9{\times}(BSA/1.2)^{0.9}$, V2 (L) = 54.5, Q (L/h) = 3.5, V3 (L) = 1080.0, $k_a(h^{-1})=0.000377$. BSA was selected as a covariate of cyclosporine clearance, which increased with an increase in BSA. Conclusion: A population pharmacokinetic model for Korean pediatric hematopoietic stem cell transplant patients was developed, and the important factor affecting cyclosporine clearance was found to be BSA. The model might contribute to the development of the most appropriate dosing regimen for cyclosporine. Further studies on population pharmacokinetics should be carried out, prospectively targeting pediatric patients.

• Korean Journal of Clinical Pharmacy
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• v.28 no.4
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• pp.279-284
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• 2018

Objective: To compare the analgesic effects and adverse drug reactions (ADRs) of fentanyl intravenous patient-controlled analgesia (ivPCA) with nefopam, a centrally acting analgesic agent with demonstrated opioid sparing activity, as compared to ketorolac in a tertiary teaching hospital. Methods: A retrospective evaluation of electronic medical records was conducted on patient records including either nefopam or ketorolac with opioid ivPCA for post-operative pain management in general surgery department from January to December 2014. The status of pain control and ADRs were collected. Results: Out of 6,330 general surgery cases, nefopam was given in 153 prescriptions (6.9%) and ketorolac in 81 prescriptions (3.6%). The level of pain control was not different between two groups (70.9% vs. 75.3%; p = 0.51), but ADRs were more frequently reported in nefopam group (9.8% vs. 2.5%; p < 0.05). New ADRs of hot flushes (n = 1) and paresthesia in hands (n = 1) were reported in nefopam group and they were unlisted in the approved package insert. No serious ADRs were reported in both groups. Conclusion: Our findings presented that nefopam showed a similar analgesic effect and higher ADR rates compared to ketorolac as an adjuvant to fentanyl iv PCA for post-operative pain management in general surgery patients in South Korea.

• Korean Journal of Clinical Pharmacy
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• v.31 no.4
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• pp.324-331
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• 2021

To investigate signals of adverse drug reactions of finasteride by using the Korea Adverse Events Reporting System (KAERS) database. This pharmacovigilance was based on the database of the drug-related adverse reactions reported spontaneously to the KAERS from 2013 to 2017. This study was conducted by disproportionality analysis. Data mining analysis was performed to detect signals of finasteride. The signal was defined by three criteria as proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC). The signals of finasteride were compared with those of the other drugs; dutasteride (similar mechanism of action), minoxidil (different mechanism but similar indications for alopecia), silodosin (different mechanism but similar indications for BPH). It was examined whether the detected signals exist in drug labels in Korea. The total number of adverse event-drug pairs was reported 2,665,429 from 2013 to 2017, of which 1,426 were associated with finasteride. The number of investigated signals of finasteride was 42. The signals that did not include in the drug label were 29 signals, including mouth dry, hypotension, dysuria etc. The signal of finasteride was similar to that of dutasteride and silodosin but was different to that of minoxidil. Early detection of signals through pharmacovigilance is important to patient safety. We investigated 29 signals of finasteride that do not exist in drug labels in Korea. Further pharmacoepidemiological studies should be needed to evaluate the signal causality with finasteride.

• Korean Journal of Clinical Pharmacy
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• v.31 no.4
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• pp.311-323
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• 2021

Objective: The disabled are in a blind spot for obtaining information on drugs, and the pharmacies' counseling on drug use is centered on non-disabled people. Few studies have investigated the current statuses of drug use by type of disability. The purpose of this study is to understand the drug use by type of disability and by life cycle of visually impaired and hearing impaired in Korea. Methods: The study participants consisted of 16 people with visually impairments, 12 people with hearing impairments. One in-depth interview was conducted per participant, and each interview was recorded and documented. Results: Common barriers against safe medication and medical service uses across disability types are 'lack of consideration and service for the disabled, limited access to medical facilities due to disability, limited access to information regarding medication use, psychological anxiety about drug use and side effects, and inconvenience regarding COVID-19 epidemic. The specific factors were 'difficulties in identifying proper medicines and following prescribed dosages' in the case of visually impaired, and 'problems with sign language interpretation system' for the hearing impaired. Conclusion: Disabled people are hindered from using medicines properly due to various factors. Based on the content derived from this study, it is necessary to eliminate the inhibition factors and devise specific measures for the safety of each type of disorder such as developing a method for medication counseling considering disabilities and establishing communication support systems.

• Korean Journal of Clinical Pharmacy
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• v.32 no.1
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• pp.1-7
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• 2022

Objective: The purpose of this study was to detect signals of Adverse Events (AEs) after varenicline treatment using spontaneous AEs reporting system in Korea. Methods: This study was conducted by Korea Institute of Drug Safety and Risk Management-Korea Adverse Event Reporting System Database (KIDS-KD) reported from January 2013 to December 2017 through Korea Adverse Event Reporting System. Signals of varenicline that satisfied the data-mining indices, proportional reporting ratio, reporting odds ratio and information component were defined. The detected signals were checked whether they included in drug labels in South Korea and United States of America (USA). Results: A total number of drug AE reports associated with all drugs in the KIDS-KD reported between January 2013 and December 2017 was 2,665,429. Among them, the number of AE reports associated with varenicline was 1,398. Eighteen meaningful signals of varenicline were detected that satisfied with the criteria of data-mining indices. Finally, two signals such as hypotonia, incorrected dose administered were not included in the drug labels. Conclusion: New AE signals of varenicline that were not listed on the drug labels in South Korea and USA were detected. However, further pharmacoepidemiological studies such as randomized controlled trial are needed to evaluate the causality of the signals of varenicline.

• Korean Journal of Clinical Pharmacy
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• v.34 no.1
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• pp.21-29
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• 2024

Background: Daytime sleepiness, a common phenomenon among adolescents focused on academics, has negative effects on aspects such as growth and overall learning. However, research on various drugs and diseases affecting daytime sleepiness is lacking in the reality. Therefore, this study aims to investigate the factors influencing daytime sleepiness in adolescents with daytime sleepiness. Methods: This study was conducted through a survey of 2,432 middle and high school students, aged 14 to 19. The questionnaire consisted of information on socio-demographic characteristics, overall health status, and sleep patterns. The Pediatric Daytime Sleepiness Scale (PDSS), translated into Korean, was used to assess daytime sleepiness. Daytime sleepiness was measured by calculating the total score for each item of the PDSS, and divided into two groups based on the cutoff value of 19, which was the upper quartile. Results: We analyzed a total of 1,770 students including 799 boys and 971 girls. Students with a PDSS score of 19 or higher made up 33.3% of boys and 66.7% of girls. In multivariate analyses, females, smoking, poor self-reported health level, sleep after 12 am, not feeling refreshed in the morning, headache, muscle pain, and scoliosis increased the risk of daytime sleepiness significantly. The AUROC of PDSS, including significant factors in multivariate analyses, was 0.751 (95% CI 0.725~0.776). Conclusions: Daytime sleepiness in adolescents affects growth, academic performance, and emotional stability. Therefore, it is important to manage medications, diseases, and other factors that affect daytime sleepiness on a social level.

• Korean Journal of Clinical Pharmacy
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• v.34 no.1
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• pp.39-61
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• 2024

Background: The Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Ministry of Food and Drug Safety (MFDS) have been implementing the expedited programs that promote the innovative approval of new medications to be used for serious diseases. The authors comprehensively investigated, analyzed, and compared the regulations and guidelines associated with the expedited programs. Methods: The expedited programs for innovative drug development and approval were searched from the homepages of FDA, EMA and MFDS. The detailed information on the regulations and guidelines associated with the programs was comprehensively extracted from various electronic repositories of each regulatory authority. The information on each program was analyzed, categorized, and compared from the points of benefits, applicability with scientific rationale, application procedure, and maintenance. Results: FDA's programs include Fast Track Designation, Breakthrough Therapy Designation, Priority Review Designation, and Accelerated Approval. EMA's regulation implements PRIority MEdicines (PRIME), Accelerated Assessment, Marketing Authorization under Exceptional Circumstances (MAEC), and Conditional Marketing Authorization (CMA). MFDS has a single Expedited Program. These programs are broadly categorized into those that 1) facilitate early and proactive communication with regulatory authorities, 2) shorten the review time after submitting a marketing application, and 3) temporarily approve a marketing authorization under certain conditions. Conclusion: Each expedited program requires a different level and amount of safety and efficacy evidence to be submitted to each regulatory authority. This article will likely provide the comprehensive information on which program provides scientific and regulatory advantages to be taken for innovative medication development.