• 제목/요약/키워드: 약학

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메타분석을 이용한 호르몬 수용체 양성/인체 상피세포 성장 인자 수용체 음성 진행성 유방암에서 사이클린 의존성 인산화효소 4/6 억제제와 방향화효소 억제제 병용요법과 방향화효소 억제제 단독요법의 임상적 유효성 및 안전성 비교 연구 (A Comparative Study on the Clinical Efficacy and Safety between Combination Therapy with CDK 4/6 Inhibitor and AI Versus AI Monotherapy in HR+/HER type2- Advanced Breast Cancer: Updated Meta-analysis)

  • 김민지;김경;조문경;손기호;백인환
    • 한국임상약학회지
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    • 제30권1호
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    • pp.1-10
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    • 2020
  • Objective: The aim of the study was to perform a meta-analysis of randomized clinical trials to compare the clinical efficacy and safety between combination of cyclin-dependent kinase (CDK) 4/6 inhibitors with aromatase inhibitors (AIs) and AIs alone in patients with hormone receptor+/human epidermal growth factor receptor type2-(HR+/HER2-) advanced breast cancer. Methods: Published clinical studies were identified through electronic database searches until February 2019. Literature qualities were assessed by the Scottish Intercollegiate Guidelines Network Checklist. Key endpoints of efficacy were progression-free survival (PFS), objective response rate (ORR), and clinical benefit (CB). Endpoints of safety were adverse events (AEs) (neutropenia, leukopenia, any grade 3/4 AEs, and serious AEs) and on-treatment death. Meta-analysis was performed using the RevMan 5.3 software. Results: The selected five studies were evaluated as "good" in quality assessment. Compared to AIs alone, the combination therapy significantly improved PFS (pooled hazard ratio=0.55; 95% confidence interval (CI) 0.49-0.62), ORR (odds ratio=1.78; 95% CI=1.49-2.13), and CB (odds ratio=1.86; 95% CI=1.51-2.28). The prevalence of AEs was significantly higher in the combination group than in the AIs alone group. On-treatment death was greater in the combination group than in the AIs alone group, although insignificant. Conclusion: The combination therapy of CDK4/6 inhibitors with AIs was more effective for the treatment of HR+/HER2- advanced breast cancer, but less safe than AIs alone. The combination therapy should be effectively managed through patient monitoring, and further studies are needed to reduce AEs in the combination therapy of CDK4/6 inhibitors with AIs.

Tacrolimus의 혈중농도 변동성이 간이식 예후에 미치는 영향 (The Effects of Intrapatient Variability in Tacrolimus Concentration on Clinical Outcomes Immediately After Liver Transplantation)

  • 김은지;김보람;조정원;이정화;이은숙;유윤미;조재영;김은경;최영록
    • 한국임상약학회지
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    • 제30권1호
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    • pp.36-43
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    • 2020
  • Background: Tacrolimus, a calcineurin inhibitor, is an immunosuppressant used in post-transplantation maintenance therapy. The drug has a narrow therapeutic range and requires periodic therapeutic drug monitoring. Although many studies have reported the effects of intrapatient variability of tacrolimus on survival, rejection, and complications in renal transplant recipients, very few studies have reported these effects in liver transplant recipients. The purpose of this study was to evaluate the effect of intrapatient variability of tacrolimus on clinical outcomes after liver transplantation. Methods: Intrapatient variability was calculated using individual, averaged tacrolimus concentrations. Patients were divided into two groups according to their median variability value: high-variability and low-variability groups. The rate of deviation from the therapeutic range, incidence of acute rejection, post-transplant diabetes, incidence of infection, and estimated glomerular filtration rate (eGFR) after transplantation were compared between the groups. Results: Of the total patients (n=82), the high-variability group (n=41) exhibited significantly greater deviation from the therapeutic range (65.92% vs. 56.84%; p<0.001). There was no significant difference in acute rejection or post-transplantation diabetes incidence or eGFR; however, the number of infection in the first 6 months was significantly lower in the low-variability group (0.4 vs. 0.9 times; p=0.039). Multiple linear regression analysis showed that the number of infection significantly increased as intrapatient variability increased (p=0.015). Conclusion: High intrapatient variability in tacrolimus concentrations was strongly associated with an increased frequency of deviation from the suggested therapeutic range and an increased number of infection.

HMG CoA-reductase inhibitors를 복용하는 환자의 잠재적 약물상호작용 연구 (Evaluation of Potential Drug-Drug Interactions in Patients Taking HMG CoA-reductase Inhibitors)

  • 이경주;김경림;성재민;유승완;이현윤;조세경;정예지;남기남;이유정
    • 한국임상약학회지
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    • 제30권1호
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    • pp.31-35
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    • 2020
  • Objective: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are frequently prescribed medications worldwide for the treatment of hypercholesterolemia. Statins are considered to be well tolerated; however, they have a potential for myotoxicity. Concomitant drugs that inhibit cytochrome P450 3A4 can increase the concentration of statins and thus the risk of developing myotoxicity. The purpose of this study was to evaluate risk factors associated with potential drug-drug interactions in patients receiving statins. Methods: The subjects of this study were patients aged more than 18 years who received at least one prescription of statins in a general hospital located in Chuncheon-si, Korea, between January 1, 2018, and March 31, 2018. Data regarding statin use and baseline characteristics was collected from the computerized hospital database. Logistic regression analysis was used to identify risk factors associated with potential drug-drug interactions. Results: A total of 1061 patients were finally included in the study. The incidence of potential drug-drug interactions was 45% in all subjects. According to the results of the multivariate logistic regression analysis, myocardial infarction as the indication of statin, arrhythmia or heart failure as a comorbidity, and aspartate aminotransferase levels higher than 40 IU/L were significant risk factors for potential drug-drug interactions in study subjects. Diltiazem was the most commonly co-prescribed drug that caused potential drug-drug interactions with statins. Conclusion: There was a considerable rate of potential drug-drug interactions in patients receiving statins. Health care professionals should attempt to reduce potential drug-drug interactions during statin administration.

국내 사람유두종바이러스백신 접종 후 자발적 이상반응 보고사례의 Brighton Collaboration 기준 활용 가능성 연구 (Patterns of Spontaneous Adverse Events Reporting on Human Papillomavirus Vaccines according to the Applicability of Brighton Collaboration Criteria in Korea from 2008 to 2017)

  • 김묘송;유승훈;박혜민;이민택;강예진;구현지;정선영
    • 한국임상약학회지
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    • 제30권1호
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    • pp.19-30
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    • 2020
  • Objective: To describe patterns of spontaneous reporting on adverse events following immunization (AEFIs) using the human papilloma virus (HPV) vaccine according to the Brighton Collaboration (BC) criteria. Methods: We used the Korea Adverse Event Reporting System (KAERS) database including vaccinations between 2008 and 2017. To apply BC criteria, we classified 58 BC AEFIs into World Health Organization Adverse Reaction Terminology (WHO-ART) codes. We applied MedDRA standard medical queries that were pre-defined as five BC AEFIs. Terminology mapping between MedDRA and WHO-ART terms was performed by three researchers. Descriptive statistics of individual case safety reports were analyzed according to BC applicability. Disproportionality analyses were performed on each BC AEFI and each preferred AEFI term according to the case-noncase approach; reporting odds ratio (ROR) and 95% confidence intervals (CI) were calculated. Results: Among the 30,266 reports of vaccinations between 2008 and 2017, 2,845 reports included the HPV vaccine. Of these reports, 1,511 (53.1%) included at least one BC AEFI. Reports from physicians or manufacturers included more BC AEFIs than from other reporters. Injection site reactions and fever were frequently reported in BC AEFIs; spontaneous abortion and ectopic pregnancy (ROR, 14.29 [95% CI, 4.30-47.49]) and vasculitic peripheral neuropathy (ROR, 8.57 [95% CI, 2.61-28.10]) showed the highest ROR. Among non-BC AEFIs, dizziness or myalgia were frequently reported; exposure during pregnancy (ROR, 23.95 [95% CI, 16.27-35.25]) and inappropriate schedule of administration (ROR, 22.89 [95% CI, 16.74-31.31]) showed the highest ROR. Conclusion: BC criteria would be applicable for labeled AEFIs, whereas analyzing non-BC AEFIs would be useful for detecting unlabeled AEFIs.

간이식 후 골다공증 관리 (Management of Osteoporosis in Liver Transplant Recipients)

  • 최호정;김보람;김윤희;이정화;이은숙;김은경;조재영;최영록
    • 한국임상약학회지
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    • 제30권1호
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    • pp.51-58
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    • 2020
  • Background: Prevention of osteoporosis and bone fracture is one of the important issues for liver transplant recipients because a long history of liver disease and lifelong use of immunosuppressants, including corticosteroids, may cause these diseases. In this study, we aimed to analyze liver recipient bone status, 10-year fracture risk, and medication history. Methods: The electronic medical records of adult patients aged >40 years who received liver transplantation at Seoul National University Bundang Hospital between January 2009 and June 2017 were reviewed retrospectively. On the basis of their bone mineral density and fracture history, their fracture risks were analyzed using the Korean fracture risk assessment tool. Results: A total of 57 liver transplant recipients were treated with corticosteroids during a mean of 8.8 months after transplantation. 30 patients (52.6%) showed bone metabolism dysfunction such as osteopenia or osteoporosis. The 10-year femoral fracture risk was 2.1%, and dual-energy X-ray absorptiometry monitoring was performed, including right before liver transplantation every 27.5±19.2 months. The mean femoral bone mineral density decreased by -7.2%±7.3%. Four patients (7.0%) had a fracture after liver transplantation. Osteoporotic fracture occurred in 3 patients with osteoporosis (25.0%). Among the osteopenia patients with moderate fracture risk who were not treated with bisphosphonate, 1 patient (12.5%) had a history of bone fracture after liver transplantation. Conclusions: Considering the deterioration of bone density and moderate fracture risk, medication for osteoporosis should be prescribed to liver transplant recipients with regular monitoring of bone density after transplantation.

치료제, 조제학 및 식물을 위한 서투인 억제제의 유용성 (A Review of Sirtuin Inhibitors in Therapeutics, Pharmaceutics, and Plant Research)

  • 이유
    • 생명과학회지
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    • 제30권1호
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    • pp.96-105
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    • 2020
  • 서투인 억제제는 유형 III 히스톤 데아세틸라제(HDAC)인 서투인을 억제하는 화합물이며, 약제학적 및 치료학적 가치를 갖는다. 합성 서투인 억제제는 효모 S. cerevisiae 에서 세포-기반 스크린을 사용하여 발견되었고 특성화되었으며 서투인의 기능과 관련된 노화, 발암 및 당뇨병을 연구하는데 사용되었다. 의학 분야에서 합성 서투인 억제제는 보다 강력한 효능과 특이성을 얻기 위해 개발되어 왔다. 니코틴아미드 및 티오아세틸리신 함유 화합물, β-나프톨 함유화합물, 인돌 유도체. 수마린, 테노빈 및 그 유사체가 개발 되었다. 서투인 억제제는 식물 발달에 영향을 미치는 것으로 밝혀졌으며 식물의 화학적 유전학에 사용되었다. 그러나, 시르티놀-내성 돌연변이 체는 알데히드 옥시다제에 대한 몰리브돕테린 보조인자의 생합성 유전자에 돌연변이가 있었다. 일부 천연 플라보노이드, 카테킨 유도체 및 퀴르세틴 유도체는 서투인 억제제로서 작용하며 치료 목적을 위한 보다 강력한 억제제를 찾기 위해 연구 되고 있다. 이 리뷰에서, 서투인을 소개하면서 치료제에서 개발된 서투인 억제제를 소개한다. 서투인 억제제인 서티놀은 식물에서 화학적 유전학에 예기치 않게 사용되었습니다. 보다 강력하고 선택적인 서투인 억제제가 치료제에서 개발되어야 하고, 약학에서 개발된 다른 서투인 억제제는 식물에서 보다 진정한 서투인을 찾기 위해 사용되어야 한다.

노인 환자에서 Vancomycin 사용과 관련한 신독성의 위험인자 연구 (Risk Factors for Vancomycin-Associated Nephrotoxicity in Elderly Patients)

  • 김하늬;김해숙;이양현;이경주;신승우;박선철;이유정
    • 한국임상약학회지
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    • 제27권1호
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    • pp.22-29
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    • 2017
  • Objective: Infection is very common in the elderly, so there is a high prevalence of antibiotics use among this population. Especially, due to the emergence of resistant bacteria, the use of vancomycin is growing. The purpose of this study was to evaluate risk factors associated with vancomycin-induced nephrotoxicity in elderly patients. Methods: The subjects of this study were patients over 18 years old who received intravenous vancomycin in a general hospital located in Gangneung-si, Korea between August 1, 2013 and July 31, 2015. Data collection regarding vancomycin use and baseline characteristics was conducted using computerized hospital database. Logistic regression analysis was used to identify risk factors associated with vancomycin-induced nephrotoxicity. Results: A total of 290 patients were finally included, and 191(66%) out of these patients were age 65 or older. The incidence of vancomycin-induced nephrotoxicity was 11.0%, 12.6%, and 7.0% in the all adult patients, the elderly patients, and the non-elderly patients, respectively. There were significant differences in comorbidities between patients with nephrotoxicity and patients without nephrotoxicity in the all adult patients, and there were significant differences in vancomycin duration, comorbidities, and number of nephrotoxic agents between patients with nephrotoxicity and patients without nephrotoxicity in the elderly patients. However, according to the logistic regression analysis, there was no significant risk factor that increases the incidence of vancomycin-induced nephrotoxicity in all three age groups. Conclusion: There were no differences in risk factors that increase the incidence of vancomycin-induced nephrotoxicity between all adult patients, elderly patients, and non-elderly patients. Further studies with larger sample sizes to identify risk factors associated with vancomycin-induced nephrotoxicity in the elderly to improve the outcome of pharmacotherapy are required.

중등도 이상의 위험 수술을 받은 환자에서 수술 전후 항혈전제 약물 사용 평가 (Evaluation of Perioperative Antithrombotic Management in Patients Undergoing Moderate to High Risk Surgery)

  • 이현아;조윤희;조윤숙;한현주;이주연;정근화;이상건
    • 한국임상약학회지
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    • 제27권1호
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    • pp.15-21
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    • 2017
  • Objective: The perioperative management of antithrombotic therapy is often challenging and it requires a fine balance between the risk of hemorrhage and thrombosis. We aimed to evaluate the antithrombotic management for moderate to high risk patients in real world setting. Methods: Among the patients who were consulted to the neurologist for the evaluation of perioperative risk from 2010 to 2012, patients undergoing moderate to high risk surgery and taking antithrombotics within 30 days were identified. We analyzed the timing of discontinuation and reinitiation of antithrombotic drugs before or after surgery as well as the status of bridging therapy. In addition, the conformity with the guideline suggested by American College of Chest Physicians was assessed. The rate of thromboembolic event and major hemorrhage were also investigated. Results: A total of 329 patients were included. The concordance rate of warfarin stop and restart time with guideline was 23.4% and 10.3%, respectively. Continuing aspirin in patients undergoing coronary artery bypass surgery or non-cardiac surgery in patients with high risk for cardiovascular events were 59.2% and 2.6%, respectively. Bridging therapy was adopted in 92.9% and 81.2% in patients who had received anticoagulant before surgery and who were at high and low risk thromboembolism, respectively. In entire cohorts, 30-day incidence of major bleeding and thromboembolic event were 31.9% and 3.0%. Co-morbid renal disease were shown as independent predictor for major bleeding (adjusted OR 2.65. 95% CI 1.33-5.28). Conclusion: The concordance rate with guideline regarding perioperative antithrombotic use was low and bridging therapy was prevalent in patients undergoing moderate to high risk surgery.

소용량 Vancomycin 주사액 조제방법의 차이에 의한 정확성 비교: 단일희석방법과 이중희석방법 (The Comparison of the Accuracy in Preparing Small Vancomycin Dosage : Single vs. Double Dilution Method)

  • 신혜영;서옥경;이숙향;신현택
    • 한국임상약학회지
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    • 제7권2호
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    • pp.86-90
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    • 1997
  • This study was to find a more accurate method fur measuring small vancomycin dosages which are commonly used in neonates by comparing single and double dilution method. For single dilution method, 500 mg of vancomycin powder was accurately measured and reconstituted with 5 ml of distilled water to make a concentration of 100 mg/ml. Volumes of 0.05, 0.1, 0.15, 0.2, 0.3, 0.4, and 0.5 ml, which equal the target dosages of 5, 10, 15, 20, 30, 40, and 50 mg, were measured using syringes made by Shina and each sample was further diluted with 2 ml of $5\%$ dextrose. The solution of 100 mg/ml concentration was further diluted with $5\%$ dextrose to make a concentration of 20 mg/ml. Volumes of 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, and 2.5 ml, which correspond to 5, 10, 15, 20, 30, 40, and 50 mg, were sampled by the same Shina's syringe as in single dilution method and then each sample was further diluted to make a total volume of 10 ml. Each sample was analyzed by HPLC. The measured dosages of each sample in both single and double dilution methods were lower than the target dosages; however, e values in double dilution method were higher than those in single dilution method for seven target dosages. Percent target dosages in single dilution method were 65 to $90\%$, while in double dilution method 91 to $94\%$. Statistically significant difference between two groups was shown in 5, 10, 15, 20, and 40 mg dosages (p<0.05). In conclusion, when preparing small vancomycin dosages lower an 20 mg $(volume{\leq}0.2\;ml)$, using Shina's syringes, the double dilution method has a closer value to the target dosage than single dilution method.

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탈리플루메이트 제제에 대한 생물학적동등성 평가 (Bioequivalence Study on Two Talniflumate Preparations Commercially Available in Korean)

  • 손의동;정지훈;김경태;조영래;민영실;송현주;제현동;임성혁;신용규;조성완
    • 한국임상약학회지
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    • 제16권2호
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    • pp.101-106
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    • 2006
  • The aim of the present study was to evaluate the bioequivalence of two talniflumate preparations. We used Somalgen tablet (Kun Wha Pharmaceutical Co., Korea.) as a reference drug for bioequivalence of Crimain tablet (Samjini Pharmaceutical Ind. Co., Korea), and performed this whole study according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty four healthy male volunteers, $22.8{\pm}2.2$ years in age and $64.6{\pm}5.3\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 370 mg of talniflumate was orally administered, blood was taken at predetermined time intervals and the concentrations of talniflumate in plasma were determined using HPLC method with UV-detector. The analysis system was validated in specificity, accuracy, precision and linearity. These items of the analysis condition in this study conform to the guideline of KFDA. The pharmacokinetic parameters such as $AUC_t\;and\;C_{max}$ were calculated using the analysis condition we established and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$ and Cmax. $Mean{\pm}SD$ of reference drug and test drug in $AUC_t\;and\;C_{max}$ value were $1.27{\pm}0.58\;({\mu}g/ml{\cdot}hr)\;and\;0.27{\pm}0.13\;({\mu}g/ml)$ and $1.14{\pm}0.46\;({\mu}g/ml{\cdot}hr)\;and\;0.26{\pm}0.10\;({\mu}g/ml)$ respectively. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log (1.25) for $AUC_t\;and\;C_{max}$, respectively. These results indicate that Samjin talniflumate tablet is bioequivalent to reference drug, Somalgen tablet.

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