Earticle

Purpose: The purpose of this study is to assess appropriateness of current standard for insurance coverage by Health Insurance Review & Assessment Service (HIRA) on chemotherapy used in the treatment of advanced non-small cell lung cancer (NSCLC), by reviewing a variety of clinical evidences, and thereby, if needed, to propose an updated evidence-based recommendations. Methods: We collected data from HIRA regarding on the insurance standard which includes the scope and conditions for coverage on systemic chemotherapy of NSCLC. We performed a search for clinical databases and examined the most current clinical evidence from clinical literature including various clinical practice guidelines. Based on the collected data the appropriateness of HIRA standard for insurance coverage of chemotherapy of NSCLC was assessed. Results: Collected data demonstrated that HIRA standard did not reflect the most current clinical practice and evidence. Some were inappropriately listed in HIRA formulary and accepted as a chemotherapy being covered by insurance, despite the lack of evidences of clinical efficacy or superiority over other chemotherapeutic agents or regimens. In addition, there seems to be a need for a modification on the standard for insurance coverage of certain newer chemotherapeutic agents based on the current accumulated data showing their clinical efficacy and benefits in the selected group of NSCLC patients. Therefore, we concluded that current HIRA standard for insurance coverage on chemotherapy of NSCLC needs to be revised and we proposed an updated recommendation based on these latest clinical evidences. Conclusion: The standard for insurance coverage of chemotherapy should be continually examined its appropriateness based on the most recent clinical evidences in a timely manner so as to provide the most effective and safe therapy to cancer patients.

목적:이 연구의 목적은 한국인 성인 환자를 대상으로 아미카신 1일 1회 요법을 시행하였을 때의 약동학적 파라미터를 평가하고, 신기능에 따른 아미카신의 약동학적 파라미터를 비교함으로써 최적의 개인화 약물요법을 설계할 수 있도록 하는 것이다. 방법:그람 음성균 감염에 대해 1일 1회 요법으로 아미카신을 투여 받았던 353명의 한국 성인 환자를 대상으로 항정상태에서 아미카신의 농도를 2회(약물 투여 전 1시간 이내, 약물투여 종료 후 0.5~1시간 이내) 측정하였다. 각 환자의 약동학적 파라미터(분포용적, 청소율, 반감기) 및 혈중 최고 농도, 최저 농도는 환자의 나이, 체중, 신장, 성별, 혈중 크레아티닌 농도, 투여된 약물용량, 측정된 약물의 혈중농도, 감염의 종류 등을 감안하여 산출하였다. 크레아티닌 청소율에 따라 환자를 4군으로 분류하여 아미카신의 약동학적 파라미터를 비교분석하였다. 결과:본 연구에서 아미카신 혈중 최저, 최고 농도의 평균 ± 표준편차는 각각 1.14±1.95 mg/L, 26.35±9.28 mg/L이며, 청소율, 분포용적, 및 반감기의 평균 ± 표준편차는 각각 55.40±23.72 mL/hr/kg, 0.35±0.12 L/kg, 그리고 5.22 ±3.34 hrs로 산출되었다. 크레아티닌 청소율에 따른 아미카신의 청소율, 분포용적 및 반감기의 유의한 차이가 관찰되었다. 종합적으로 아미카신의 혈중 최저 농도는 크레아티닌 청소율이 40 mL/min 미만인 경우 40 mL/min 이상인 경우에 비해 유의하게 증가하였다. 결론: 아미카신의 약동학적 파라미터들은 신기능에 따라 유의한 차이가 있으므로 최적의 치료효과를 위해서는 환자의 크레아티닌 청소율에 따른 개인화 약물요법이 필요하다.

암로디핀과 레파그리니드의 병용은 당뇨병의 합병증으로인한 고혈압 유발 시 병용 처방될 수 있다. 암로디핀과 레파그리니드의 약동학적 상호작용 연구를 위하여 암로디핀 (0.1 및 0.4 mg/kg) 과 레파그리니드를 흰 쥐에 경구(0.5 mg/kg) 및 정맥 (0.2 mg/kg) 투여하여 연구를 실시하였다. 암로디핀이 cytochrome P450 (CYP) 3A4 활성과 P-glycoprotein (P-gp)의 활성에 미치는 영향도 평가하였다. 암로디핀의 CYP3A4의 50% 효소활성억제는 9.1 μM 이었다. 암로디핀은 P-gp의 활성에는 영향을 미치지 않았다. 암로디핀 (0.4 mg/kg)은 레파그리니드의 혈장곡선하면적(AUC)과 최고혈장농도 (Cmax)를 40.2% 와 22.2% 각각 유의성 (p < 0.05)있게 증가시켰다. 따라서, 레파그리니드의 상대적생체이용률 (RB)은 암로디핀과 병용투여 시 1.18-1.40 배 증가되었으며, 또한 레파그리니드의 절대적생체이용률(AB)은 대조군과 비교하여 41.0% 유의성 있게 증가되었다. 경구 투여 시와는 대조적으로, 암로디핀은 정맥 내로 투여된 레파그리니드에서는 약동학적 파라미터에 어떤 영향도 미치지 않았다. 따라서 암로디핀이 레파그리니드의 생체이용률을 증가시킨 것은 신장배설 감소 또는 P-gp 활성억제 보다는 암로디핀이 소장 또는 간장에서 CYP3A4을 억제시켰기 때문으로 사료된다. 암로디핀과 레파그리니드의 병용투여 시 레파그리니드의 용량을 조절하는 것이 안전하다고 사료된다.

Entecavir is a potent and selective guanosine analogue that has demonstrated a significant antiviral efficacy against hepatitis B virus (HBV). The aim of this study was to evaluate the safety and pharmacokinetic profile after a single dose of entecavir 1 mg administration in Korean healthy male subjects. Eight volunteers were enrolled. After a single dose of 1 mg entecavir was orally administered, blood samples were collected at specific time intervals from 0-168 hours. The plasma concentrations of entecavir were determined by LC-MS/MS. The pharmacokinetic parameters were determined from the plasma concentration-time profiles. The mean values for AUClast and AUCinf were 14.84±7.81 ng·hr/mL and 20.71±8.80 ng·hr/mL, respectively. The mean value for Cmax was 9.19±4.91 ng/mL and median value for tmax was 0.58 hr. No adverse events were reported by subjects or found on analysis of vital signs or laboratory tests. The results are suggested to be useful in clinical trials of entecavir in Korean subject including bioequivalence study.

배경: 약물로 인한 Clostridium difficile-associated diarrhea (CDAD)는 널리 알려져 있으며 우리나라에서 항생제와 프로톤 펌프 억제제 소모량을 고려할 때 질환 치료과정에서의 CDAD 발생빈도 및 CDAD 유발 이전에 투여한 약물의 사용빈도와 CDAD의 치료방법을 조사할 필요성이 있다. 방법: 경상대학교 병원에서2011년 1월부터 6월까지의 입원환자를 대상으로 대변 독소 검사에 의해 CDAD로 판명된 환자의 성별, 연령분포, 질환명, 입원병동, 재발률을 조사하였으며 CDAD 판명이전에 투여한 약제 및 CDAD 판명 후 치료약제를 조사하였다. 결과: 연구기간 동안 CDAD 대변 독소 검사 의뢰된 환자수는 1,500명이었으며 CDAD 양성은 111명(9.3%)이었고, 재발은 29명(26.1%)이었다. CDAD를 주소로 입원한 환자는 17명 (15.3%)이었고, 나머지는 입원기간 중에 발생하였다. CDAD 양성인 환자의 연령대는 60대에서 32.4% (36/111명) 이었고, 내과병동에서 34.2%를 나타내었고, 재발률은 외과계 병동에서 41.4%로 가장 높게 나타났다. CDAD 환자의 17% (19/111명)은 항암제 투여 동안 발생하였으며 CDAD 발생 전 사용약물로는 세팔로스포린계 항생제가 162회로 가장 빈번하게 사용 되었으며, 히스타민2 수용체길항제 107회, 스테로이드 82회, 비 스테로이드 항염제 79회, 프로톤 펌프 억제제 77회, 하제 59회, 항암제가 33회 처방되었다. CDAD 치료약제로는 8종의 약제가 241회 처방 되었으며 metronidazole이 99회로 가장 빈번하게 사용되었고, vancomycin이 37회로 나타났다. 결론: 입원환자에 있어서 CDAD양성은 특히 고령의 암환자가 많아 항암제 투여 시에는 CDAD 발생에 주의해야 할 것으로 보인다. CDAD의 치료약제로는 metronidazole이 vancomycin 보다 많이 사용되는 것으로 나타났다.

This study measures seriousness of adverse drug reactions (ADRs) among Korean physicians and pharmacists using two times surveys based on Delphi technique. Each participant scored 20 ADR terms on a scale of one to ten (10 being the most serious). We repeated the exercise for the 49 first survey respondents and 32 re-evaluated score. We compared the results of our survey with those of WHO CIOMS (Council for International Organization of Medical Sciences) working groups members conducted in 1995. The overall mean ADR seriousness score was 6.49 for Koreans and 5.12 for WHO CIOMS members, presenting Korean experts perceived more seriously for each ADR. Mean score changes for the same respondents showed similar trends regardless of access to the first survey results. There were no statistically significant score differences between the physicians and the pharmacists. The high consensus of seriousness for each ADR between the Korean experts and the WHO CIOMS members implies that the similar results are reproducible, suggesting the possibility of developing standardized tools for measuring the seriousness of individual ADRs in the future.

낙상은 노인의 건강을 위협하는 가장 심각한 문제 중의 하나이며, 조기사망, 신체손상, 운동장애, 심리학적 기능장애를 유발하는 원인이기도 하다. 본 연구의 목적은 국내 노인전문 요양병원 입원 환자들의 의약품 사용이 낙상에 미치는 영향을 평가하는데 있다. 후향적으로 원내 의무기록 정보를 이용하여 환자-대조군 연구를 수행하였고, 2008년 1월부터 2010년 12월까지 3년 기간에 입원한 65세 이상을 대상으로 하였다. 입원기간 중 낙상을 경험한 34명의 노인환자들을 환자군으로 선택하였으며 낙상을 경험하지 않은 68명의 노인환자들을 무작위 추출하여 1:2의 환자군:대조군 비율로 연구 대상 환자들을 선정하였다. 환자군이 복용한 의약품을 대조군이 복용한 의약품과 비교하였으며 각 계열별 의약품과 낙상위험도 관계를 평가하였다. 두 그룹간의 인구통계학적 특성은 유사하였고 연령, 성별, 복용 의약품수, 고혈압 유무, 혈중 크레아티닌 수치, 혈중 나트륨 수치, 혈압 또는 심박수에 유의한 차이는 없었다. 항히스타민제와 본 연구에서 유일하게 기타 수면보조제로 분류된 졸피뎀이 유의하게 낙상위험도를 증가시켰다.

Objective: To examine the drug use (prescribing) pattern of serious drug-drug interactions (DDIs, contraindicated drug interactions) using real world data. Prescription patterns were examined in terms of dispensing types. Method: Retrospective drug utilization review (DUR) study was performed. One hundred and six datasets of serious DDIs (DDI pairs) were determined among DDI datasets that Ministry of Health & Welfare announced for the DUR system from 2004 to 2005. Electronically transacted ambulatory patients’prescription database to Health Insurance Assessment and Review Services (HIRA) from July, 2005 to June, 2006 was collected with personal information deidentified and analyzed in terms of types of dispensing as a contributing factor. Results: After prescription data analysis per each patient, total number of DDI cases using 95 DDI pairs was 5,511, which accounted for 2.6 cases per patients. DDI cases between two drugs from each of community pharmacy dispensing-type prescription were considerable (63% vs. 24% in those from each of in-institutional dispensing-type prescription and vs. 13% in those from a community pharmacy dispensing-type prescription and an in-institutional dispensingtype prescription). Conclusions: DDI cases from different prescribers were found to be significant. Thus, the concurrent DUR process between prescriptions from different physicians and institutions should be implemented for the safe drug use.

Omega-3 fatty acids are a specific type of unsaturated fat that the body cannot manufacture on its own, so they must be obtained from food which is essential fatty acids (EFAs). Omega-3 fatty acids consist of three types which are a-Linolenic Acid (ALA), Eicosapentaenoic (ELA), and Docosahexaenoic Acid (DHA). Especially, EFAs help to prevent skin and hair drying, acne, eczema, prevention from allergies, brittle nails, rashes, and tiny lumps. The aim of this study is to investigate improvement and protection for hair damaged by chemical treatment with omega-3 formulated shampoo. We selected virgin hair sample and divided into two groups for bleaching once and three times and then damaged hair by changing the number of hair bleaching (twice with interval of 15 minutes). Each bleached hair was treated by five different kinds of shampoo (Control, Horse shampoo, DHA shampoo, EPA shampoo, Omega-3 shampoo mixture). Apart from this, EPA/DHA 2, 5, 8, 10 and 12% shampoo were prepared and treated to hair for comparing rate of progress in damaged hair. To quantify improved condition of damaged hair, we performed Scanning Electron Microscope (SEM) for ultrastructure of damaged hair fraction, measurement of thickness change and BCA Protein Assay for recovery rate of damaged hair. The moisture in hair was measured by Thermal analysis machine. In results, we observed the particle of hair surface damaged by bleaching treatment were well improved with treatment with EPA and DHA shampoo. Also, quantity of protein was lowered with higher concentration of EPA & DHA i.e., 8 and 12 % then compared with horse oil shampoo in three times treatment group. It shows that bleached hair have been recovered by treating rapidly and get protective coat. In conclusion, EPA and DHA shampoo improved damaged hair, especially with EPA / DHA 12% shampoo. Also, EPA shampoo could protect the damaged hair depending on increasing concentration of EPA. Therefore, we conclude omega-3 shampoo could make damaged hair protect and get healthy hair environment.

이 증례는 드물게 보는 경우로 simvastatin과 gemfibrozil을 오랫동안 함께 복용했음에도, 특이한 문제가 발현되지 않았지만, 이들을 warfarin와 함께 치료하는 경우, 아주 높은 alanine aminotransferase (ALT), aspartate aminotransferase(AST) 혈중 농도, rhabdomyolysis, 급성 신장 장애가 발생하였다. 그 후, Simvastatin와 gemfibrozil을 복용 중단시켰더니, ALT/AST는 빠르게 정상수치로 돌아온 경우이다. 이 증례 보고서는 의료인들에게 simvastatin과 gemfibrozil을 함께 혹은 따로 warfarin과 함께 복용시켜 치료할 경우, creatine phosphokinase (CPK) 와 creatinine 혈중 수치들을 포함하여 ALT/AST 농도들을 주의 깊게 모니터하도록 경각심을 주고자 한다.

We report an unusual case of lupus flare induced by intravenous vancomycin in a patient with systemic lupus erythematosus. Due to methicillin resistant staphylococcus aureus in wound culture, intravenous vancomycin was administered to the patient. The patient had been on vancomycin for several days then she experienced fever, malar rash, and vomiting. Based on laboratory results, it was confirmed as lupus flare. Oral prednisolone was given to the patient for symptom control. However, when vancomycin was readministered, the patient had similar symptom to the previous one more intensively. Vancomycin was stopped then the patient became stable. This case report demonstrates that intravenous vancomycin may manifest as lupus flare in patients with systemic lupus erythematosus.

Vaccines are products for immunization which can provoke antibodies by eliciting immune reponses without causing disease and have played an important role in preventing fatal and contagious diseases as well as H1N1 influenza. They are classified by two following categories; lived attenuated vaccine and killed vaccine and currently commonly using vaccines are BCG, diphtheria, tetanus, mumps, measles, rubella, polio, Haemophilus influenza type b, hepatitis B, influenza etc. All vaccines must be used correctly to reach optimal therapeutic goals and also informed well to patients to decrease potential problems. In order to do, pharmacists must have good knowledge of vaccines. The purpose of this study is to evaluate the necessity of vaccine education for pharmacists and develop a vaccine leaflet for patient counseling. We have performed a survey with questionnaire for a total of 176 pharmacists and nurses(hospital pharmacists, n=65; community pharmacists, n=50; hospital nurses, n=61) from January 27th to March 12th, 2010. The questionnaire includes items about vaccine education and counseling and 12 quizzes to evaluate responders' knowledge of vaccines. We used the SPSS(Version 12. for windows) program to analyze the data. In results, 94.9% of all responders said they had not been educated on vaccines. And only 1.1% of all responders said they know about vaccines enough to counsel patients. Pharmacists who have an experience recommending vaccines to other people are 21.7%. On the other hand, nurses who have an experience recommending vaccines to other people are 55.7%(p=0.000). The mean number of correct answers at the 12 quizzes are followings; hospital pharmacist, 8.1; community pharmacist, 6.1, hospital nurses, 6.2(p=0.000). A vaccine leaflet for patient counseling is developed with several references. In conclusion, due to no opportunity of vaccine education, pharmacists have no confidence to counsel patients and lack of knowledge of vaccine. But importance of vaccine's role is increasing, pharmacists should counsel patients in vaccination. So they need vaccine education and a vaccine leaflet will be helpful for their counseling.