Earticle

목적: 이상지방혈증 환자의 치료는 우선적으로 저밀도지단백을 감소시키고, 저밀도지단백이 목표수치에 도달한 이후 에 도 혈중 중성지방이 높을 경우 nicotinic acid 또는 fibrate를 사용하도록 권장되고 있다. 본 연구는 이상지방혈증이 있는 환자에서 acipimox의 효과를 fenofibrate와 비교하여 분석하고자 시행되었다. 방법: 본 연구는 서울에 있는 한 3차 대학병원의 환자를 대상으로 후향적으로 의무기록을 분석하여 시행되었다. 혈 중 중성지방 농도가 200 mg/dL 이상으로써 acipimox 또는 fenofibrate를 신규처방 받은 환자를 대상으로 각각의 약 물이 지단백에 미치는 영향을 36주간 추적하여 비교분석 하였다. 결과: Acipimox를 투여 받은 환자 41명, fenofibrate를 투여 받은 환자 62명이 모집되었으며, 각각의 약물을 복용한 환자군의 기본적인 인구학적인 특성은 유의하게 상이하지 않았다. 3개월 간의 약물투여 후 두 약물군 환자 모두에서 총콜레스테롤(p < 0.05) 및 저밀도지단백(p < 0.001)이 약물투여 전과 비교하였을 때 유의하게 감소하였고, 고밀도지 단 백은 모든 환자에서 유의하게 증가하였다(p < 0.05). 한편 중성지방 감소율은 acipimox군이 fenofibrate군에서보다 더 크게 나타났다(p < 0.05). 약물유해반응의 빈도는 두 약물군 간에 유의한 차이가 없었다. 결론: 총콜레스테롤, 저밀도지단백 콜레스테롤 등을 감소시키거나 고밀도지단백 콜레스테롤을 증가시키는 효과는 acipimox와 fenofibrate가 유의하게 다르지 않았으며, 중성지방을 감소시키는 효과는 acipimox가 fenofibrate보다 우 월 하였다.

Methoxy polyethylene glycol-epoetin beta (MPG-EPO), a continuous erythropoietin receptor activator, is a new erythropoiesis- stimulating agent with a long half-life. The purpose of this prospective study is to assess the effects of oncemonthly subcutaneous MPG-EPO on hematological responses and nutritional status in peritoneal dialysis patients. Forty four patients undergoing stable peritoneal dialysis were enrolled into the study. Darbepoetin alfa therapy, in peritoneal dialysis patients, was converted to the monthly administration of subcutaneous MPG-EPO for 6 months. The starting dose of MPG-EPO was based on the previous weekly dose of darbepoetin alfa. The dose adjustments were performed to maintain the hemoglobin (Hb) levels in a target range of 10.5-11.0 g/dL. If the Hb levels exceeded 11.0 g/dL, MPGEPO was temporarily interrupted for 1 month. The mean Hb levels were stable with the values of 9.5±1.1 g/dL at baseline, and 10.4±0.9 g/dL at the 6th month after conversion. The mean differences in the changes of Hb levels between the baseline and the 6th month were 0.9±1.4 g/dL, which was statistically significant. However, the mean differences of iron, transferrin saturation and ferritin concentrations were not significant. It did not show significant differences in the changes of the nutritional parameters. These results suggest that the once-monthly subcutaneous administration of MPGEPO for 6 months effectively maintains the Hb levels and nutritional status in peritoneal dialysis patients. Taken together, the once-monthly subcutaneous administration of MPG-EPO was practical and might improve the clinical compliance for the management of renal anemia in peritoneal dialysis patients.

Nonsteroidal antiinflammatory drugs (NSAIDs) are used in the treatment of extensive diseases related to various symptoms; inflammation, pain and fever. NSAIDs work by blocking prostaglandin synthesis, but adverse drug events (ADEs) have been increasing dramatically such as gastrointestinal bleeding, perforation and stenosis, a kind of serious ADEs. Therefore, NSAID-related ulcer complication guidelines have been announced containing various risk factors and symptoms. Thus, this study aims to evaluate of NSAID usage and appropriateness for prevention of NSAID-related ulcer complication based on American journal of gastroenterology (AJG) guideline 2009. Further, the study suggests Korean guideline for prevention of NSAID-related ulcer compared to AJG guideline. For this study, data was collected through electronic medical record (EMR) at Seoul national university of Bundang hospital. The primary end point was a composite of NSAID-related ulcer risk factor, types of NSAIDs, co-prescribed NSAID ulcer prevention drugs and NSAIDrelated ulcer after taking NSAID. The risk factors include over 65 years, high dose NSAID, previous ulcer history and taking drugs (e.g. aspirin, anticoagulant and steroid) causing ulcer. If a patient has 3 or 4 factors, that patient was classified high risk group. And if 1 or 2 factors that patient was classified moderate risk group. The patient who has no risk factor was in low risk group. I studied 8,120 patients who received NSAID from 1 January 2009 to 31 December 2009. High risk group was 16(0.2%), moderate risk group was 4,364(53.7%), and low risk group was 3,740(46.1%). The results show that high risk group should be prescribed COX-2 inhibitors with ulcer prevention drugs, and moderate or low risk group need traditional NSAIDs with ulcer prevention drugs. This may be different with 2009 AJG guideline because AJG guideline suggested taking COX-2 inhibitor alone in moderate group or taking traditional NSAID alone in low risk group could get higher ulcer complication. The results indicated that choosing preventive drug is important in case that how many risk factors the patients have. The proper drugs would be helpful for safe and effective NSAID usage in each patient group.

Kidney and liver are the major organs of metabolism and excretion of drugs. Renal and Hepatic impairment may affect the pharmacokinetics/pharmacodynamics and the safety of drugs. Adjusting the dosage based on organ function is the essential role of pharmacists. However, differences have been noted on the recommended dosage among the literatures. We compared and analyzed the recommendations of 4 literature sources which are commonly used for dosage adjustment. From April, 2011 to August, 2011, we selected data on recommendations for dosage adjustment for impaired renal and hepatic function of 100 drugs through a protocol. We analyzed the definition terms of renal and hepatic impairment, recommendations for dosage adjustment, evidenced references in four literature sources: Korean National Formulary (KNF), American Hospital Formulary System Drug Information (AHFS), Micromedex (MM) and Drug Prescribing of Renal Failure (DPRF). We further examined the data homogeneity by comparing how drugs that required no adjustment according to one source were categorized by the other. Sources use different definition terms among themselves except DRPF. Presence or absence of evidenced references about renal/hepatic functional states are KNF (0%/0%), AHFS (78%/ 62.6%), MM (87.5%/65.6%) and DPRF (93.2%/no recommendation) respectively. Recommendations of specific dosage and dosing interval are KNF (24%/13%), AHFS (39.6%/12.1%), MM (50%/17.7%), and DPRF (55.4%/no recommendation) respectively. Regarding the data homogeneity, the differences were remarkable. Drugs with no adjustment according to AHFS were categorized to be adjusted/ contraindicated by KNF, MM, DPRF and the values were (44%/5.6%), (22%/ 0%), and (36%/0%) in renal function, (39%/6.5%), (19%/3.2%), and (no recommendation/no recommendation) in hepatic function respectively. Our study shows remarkable definite variation in definitions and recommendations about definition terms, information of dosage and interval, presence or absence of evidenced references. Especially for KNF, quantitative recommendations on dosages and dosing intervals should be made in the near future. To maximize the drug effect and safety and to minimize the heterogeneity of the literature sources, reviewing at least two sources are suggested when recommending the proper dosage adjustment based on organ function.

Purpose: The purpose of this study was to elucidate the effect of dissolved oxygen in alcohol to blood pressure of healthy persons. Methods: Subjects (n=30) were randomized in a double blind crossover study to receive 120 mL, 240 mL, 360 mL of alcohol (Korean spirit, 19.59 v/v%, dissolved oxygen is 8 ppm and 20 ppm). Blood alcohol concentration (BAC) and blood pressure were measured applying Lion SD-400 Alcolmeter® Breathalyser and Tensoval duo control. Pharmacokinetic parameters (Cmax, Tmax, AUClast, Kel, Vd, Clearance) were calculated using Winnonlin ® program. The difference of parameters and values were analysed by student t-test using Microsoft® Excel program. Results: The AUClast values of 8 ppm group and 20 ppm group in 240 ml administration were 6.15±2.60 cg·min/ml, 5.33± 1.84 cg·min/ ml (p<0.05) and those in 360 mL were 11.93±5.70 cg·min/ml, 10.33±4.60 cg·min/ml (p < 0.01), respectively. Thus, the AUClast was significantly decreased. On the other hands, there was a significant change in systolic blood pressure (SBP) after alcohol administration. All measured value after 360 mL of alcohol administration was significantly decreased (p < 0.01). Conclusions: The dissolved oxygen in alcoholic beverage has no effect on blood pressures but the alcohol administration has an effect on blood pressure. Thus, SBP can be used as a biomarker of alcohol administration and utilized in PK/PD modeling of alcohol.

Background: Valproic acid is widely used in the treatment of generalized tonic-clonic and partial seizures. The carbapenem class is the most potent and widest spectrum of antimicrobial activity. Concomitant administration of carbapenems and valproic acid has been reported to decrease the serum concentration of valproic acid, which is sometimes associated with seizures. The purpose of this study is to evaluate the changes in valproic acid concentration and half life and the frequency of seizure during concomitant administration of valproic acid and carbapenems. Method: This study was performed retrospectively on total 40 cases with identified valproic acid concentration during concomitant administration of valproic acid and carbapenems at Kangbuk Samsung Hospital from February 1st, 2006 to October 31st, 2011. Patients were classified into 3 groups: ertapenem group (n=14), imipenem group (n=12), meropenem group (n=14). Results: The mean serum concentrations in each group during combined treatment were 9.50±8.84, 21.88 ±8.17 and 10.62±8.67 mg/L, respectively (p < 0.001). The mean half-lives in each group during concurrent use of valproic acid and carbapenems were 3.18±0.81, 4.63±1.97 and 2.67±1.69 hr, respectively (p < 0.001). The valproic acid serum concentration decreased by 75.5%, 54.1% and 84.1% and the half-life of valporoic acid decreased by 65.6%, 35.7% and 73.5%, respectively. Total cases with seizure were 12(30%) with 5(35.7%) in the ertapenem group, 3 (25.0%) in the imipenem group and 4(28.6%) in the meropenem group (p=0.911). There were no specific factors to influence on seizure development during combined treatment. Conclusion: Concurrent use of carbapenems and valproic acid should be avoided. If concomitant administration is essential, very close serum concentration monitoring and clinical observation are necessary.

In recent years, national health insurance(NHI) coverage had been expanded gradually for cancer as a severe disease requiring high level of medical expenditure, to reduce patient's financial burden. But, subjective burdens level for outof- pocket(OOP) money expense are still considerable owing to high medical cost and decent numbers of services not covered by benefit plan. This study aimed to investigate OOP medical expenditures and identify factors influencing subjective financial burden in cancer patients. A 28-items questionnaire for self-reporting by responders was designed to satisfy study goal and finalized following by one pilot study and experts' verification process. Subjects were enrolled during July to October 2010 through regular meetings organized by five patient or patient-advocacy groups had acknowledged the study purpose. Subjects who aged 20 or more, have histories of cancer diagnosis and anticancer drug use, and voluntarily agreed to participate in this study were recruited. Total 107 subjects included in the analysis have cancer lesions in breast, colon, kidney, liver or stomach at the stages from I to IV. Approximately 73% of them has passed less than 5 years since cancer diagnosis. For the OOP medical expenditure regarding cancer, less 6 million won was in 31%, 6-15 million won in 35% and more than 15 million won in 28% of responders, and more than half responders(58%) felt financial burden subjectively. 63% of responders had subscribed commercial insurances, resulting in money receipts of more than 10 million won since cancer diagnoses in 76% of responders. Logistic regression results showed significant differences in subjective OOP financial burden level depending on gender, household income level, benefit type, commercial insurance money receipt degree, year cancer diagnosed, cancer lesion, therapy type, duration of anticancer drug use, drug listing in national formulary, total OOP medical expenditure and total OOP anticancer drug expense. They had mixed feelings both wishes to expand NHI coverage to reduce financial burden(70%) and no willingness to increase premium(59%). This result suggested that NHI might direct future strategies to reduce absolute total OOP medical cost and expand benefit plan coverage in higher burden groups in particular.

Ulcerative colitis (UC) is characterized by a life-long chronic course with remissions and exacerbations. Use of biological therapies may reduce or delay the surgical procedures in patients with UC. The aim of this study was to determine the impact of infliximab (IFX) use on the rate of remission, surgical interventions, and the effect on quality of life in patients with moderate to severe UC. Literature was searched for studies that investigated the efficacy of IFX on the rate of remission, colectomy and quality of life (QoL) between January 1990 and June 2012 at MEDLINE, January 1988 and June 2012 at EMbase and others. Eleven trials were included in the meta-analysis; divided into placebo controlled 8 trials and intravenous corticosteroid controlled group 3 trials. In comparison to placebo control groups, patients who received IFX had an odds ratio (OR) of 3.712 (95% CI: 2.714, 5.079) for the short-term clinical remission, and 3.053 (95% CI: 2.044, 4.559) for the rate of long-term remission. In colectomy rate and quality of life (QoL), odds ratio were 0.566(95% CI: 0.387, 0.827) and 0.658 (0.505, 0.811) respectively. Any adverse reactions including infections, infusion reaction, rash and arthralgia were equivalent in both groups. Compared with intravenous corticosteroid controlled group, patients who received IFX had lower remission rate with short-term odds ratio 0.227 (95% CI: 0.033, 1.556) and longterm odds ratio 1.054 (95% CI: 0.317, 3.502) respectively. However, statistical significance was not showed with both two analyses. The higher adverse drug reaction (ADR) rates were occurred in the corticosteroid controlled groups. 73.3% of patients treated corticosteroid reported Cushing-like syndrome with moon face. In conclusion, IFX does increase remission rate and decrease the rate of colectomy in patients with UC without elevating any adverse reactions significantly. IFX also improves QoL in moderate to severe UC patients. It would not exceed the efficacy of intravenous corticosteroid, whereas intravenous corticosteroid also reported high rate of adverse reactions.

The objective of this study was to investigate drug classification system in Korea and other developed countries. Laws and regulations of Korea regarding the system were retrieved from sources posted in Ministry of Government Legislation. We also reviewed previous research reports performed as part of government’s effort to reform the system The system in the foreign countries was retrieved from the official homepage operated by each country’s government. There have been two research funded by Korean government, which strongly suggested that the system should be reformed. However, we found that the system was never reformed and still effective. Drug classification system in US and most western countries consists of two categories, i.e., prescription drugs and non-prescription drugs except UK, which classifies into three categories: Prescription Only Medicines, Pharmacy Medicines, and General Sales List Medicines. Interestingly, in Japan, non-prescription drugs are further classified into three groups: Group 1, 2, and 3. Recently, Ministry of Health and Welfare (MOHW) in Korea proposed a plan to reclassify all the approved drugs according to purportedly rational and scientific criteria. However, the plan does not include reform of the existing laws and regulations, which appears that it is just one-time action rather than a sustainable administration backed up by law. Therefore, it is recommended that Korean MOHW take appropriate action on laws and regulations with regard to the system to meet global harmonization standard.

The definition of anaphylaxis is 'a serious, life-threatening generalized or systemic hypersensitivity reaction' and is considered as the life threatening adverse drug reaction. We experienced a case of cefotetan induced anaphylaxis with negative pre-skin test, used for surgical prophylaxis. A 82-year-old female was scheduled for total knee replacement therapy. She had no previous history of allergy and her skin test results were also negative. On her right knee surgery, she underwent cefotetan therapy as a surgical prophylaxis for a week with no problems identified. Next left knee surgery, she also received the prophylaxis of intravenous cefotetan. However, a few minutes later, anaphylactic reaction developed with vomiting, severe hypotension, bronchospasm, and dyspnea. After immediate intensive care treatment, she recovered without significant complications. Though commonly used laboratory data in case reports, such as the specific IgE, tryptase, histamine, or allergic skin prick test were limited, we successfully confirmed anaphylaxis based on clinical criteria for diagnosing anaphylaxis based on WAO 2011 guideline with through concurrent patient°Øs medical history review and the process of identifying the causes.

현재 HIV(human immunodeficiency virus) 감염에 대하여 보다 많은 효과적인 약물치료법이 가능하다. Highly active antiretroviral therapy (HAART)로 언급되는 이 치료법은 항 HIV치료제의 다양한 병용법으로 구성된다. 그러나, 최근에 이렇게 치료된 환자들에게 중요한 독성들(toxicities)로서 빈번하게 상당한 지질이상과 혈중당의 항상성 조절장애와 연관 된 몸의 지방 분포 비정상으로서 나타나는, 광범위한 대사성 합병증(metabolic complications)이 출현해왔다. 이러한 합 병증의 관리는 표준적인 치료 중재(interventions)와 연관하여 지질과 당 대사와 관련된 항 HIV치료제의 특성 있는 효 과를 이해하면서, 항 HIV 약물들을 조절하는 것을 포함한다. 본 증례는 항HIV 약물요법과정에서 나타난 상당한 지질 이상, 매우 높은 LDL 수치와 높은 TG수치에 따르는 후속 약물요법을 보여주며, 개별화된 항 HIV 약물요법을 수행 하면서, 대사성 합병증에 관련된 수치의 검사와 주기적인 약물치료과정의 모니터링을 권하여 HIV에 감염된 환자들의 효과적인 치료를 향상시키기 위한 것이다.