Earticle

Drugs mostly represent an efficacy or an adverse effect according to their dosage and/or plasma concentrations. Therefore, to investigate the pharmacokinetic behavior of drugs including herbal medicines is necessary both to maximize the drug action and to minimize the adverse effect. To date, pharmacokinetic studies of herbal medicines have been conducted by some experts in this field on the bases of science and knowledge in Korea. On the other hand, in advanced countries, a typical series of pharmacokinetic studies has been conducted by using a harmonized guidance established. Consequently, an administrative support on these studies has to be needed in Korea as well. This study aimed to establish a draft guidance on pharmacokinetic studies of herbal medicines in non-clinical and clinical studies. Literatures previously published as well as guidances in the US, Europe and Japan were summarized for the present guidance. Effect of herbal medicines was listed on the proteins in charge of drug metabolism and transportation, as well as on the pharmacokinetics of chemical drugs. The present suggestion might be helpful to proceed pharmacokinetic studies of herbal medicines efficiently, and further polish should be needed in terms of an administrative point of view.

서 론: 중환자실에서 집중적 인슐린 요법에 의한 평균혈당강하는 사망률을 감소시키는 것으로 나타났으나 이로 인한 저혈당 및 혈당변동은 새로운 문제로 대두되고 있다. 본 연구에서는 혈당과 관련한 여러 요인들이 사망에 미치 는 영향을 규명하고 적정 혈당치를 확인하고자 하였다. 연구방법: 2008년 2월부터 7월 사이인 6개월 동안 서울아산병원 외과계 중환자실에서 4일 이상 재실한 18세 이상의 성인 환자를 대상으로 전자 의무기록 조사를 통해 후향적으로 연구가 진행되었다. 연구를 위해 환자의 인구학적 특 성, 수술의 종류, 중환자실에서의 재실기간, 사망여부, 스테로이드 사용 유무, 기계적 인공호흡기의 사용유무, 신대체요 법의 사용유무, 혈당치, 재실기간 중 스테로이드 사용유무와 인슐린 양, 입원 후 첫 24시간 동안의 포도당 주입속도, 입원 후 2일 이내와 그 이후에 발생한 균혈증 감염, APACH II와 SOFA 점수를 조사하였다. 혈당수치는 각각의 환자에서 중환자실 입실 후 가장 처음 측정된 혈당, 재실기간 중 가장 높은 혈당과 가장 낮은 혈당수치를 조사하였 고 중환자실 전체 재실기간 동안 혈당수치의 평균과 변동계수를 계산하였다. 이상의 혈당관련지표를 포함한 인자들이 일차 종속변수인 사망에 어떠한 영향을 주는지를 환자를 생존군과 사망군으로 나누어 분석하였고 ROC (receiver operator characteristic) 곡선을 사용하여 혈당지표와 APACH 및 SOFA 점수의 cut-off치를 구하여 이로부터 단변량 및 다변량 분석을 시행하였다. 결 과: 연구에 포함된 환자는 170명 이었고 그 중 23명이 연구 기간 중 중환자실에서 사망하였다. 생존자에 비 해 사망자의 최대혈당은 유의적으로 높았고 최소혈당치는 유의적으로 낮아 높은 변동계수를 보였다. ROC곡선으로부터 산출된 혈당치들의 cut-off 수치는 최소혈당치 70 mg/dL, 변동계수 25%, 최대혈당치 250 mg/dL, 평균혈당치 150 mg/ dL이었다. 다변량분석에서 최소혈당이 70 mg/dL 보다 큰 경우가 낮은 경우에 비해 오즈비가 0.922(95% 신뢰구간 0.881-0.965)로 유의성 있게 낮았으며 변동계수가 25% 보다 높은 집단의 경우 그보다 낮은 집단에 비해 오즈비가 1.121(95% 신뢰구간 1.017-1.236)로 유의성 있게 높았다. Kaplan-Meier 생존분석 결과 최소혈당치 70 mg/dL와 변동 계수 25%에 따라 생존기간에 유의성 있는 차이가 나타났다.(각각 P < 0.001, P < 0.05) 결 론: 고혈당 발생의 감소뿐 아니라 최소혈당치를 70 mg/dL 이상으로 유지하면서 변동을 최소화하는 것이 외과 계 중환자실에서의 사망률감소를 위한 중요한 요인임을 알 수 있었다.

Objectives: We developed a registry guidance to provide a standard for data collection, analysis and methodical management of information on the influence of drug exposure on pregnant women and fetus. Methods: We surveyed guidances and regulations of clinical trials and the pharmaceutical affairs law, compared them with Pregnancy Exposure Registry of other countries and in addition, investigated related references. We found the flaws of the present registry and supplemented it based on better results from other countries. Results: We developed a concrete and detailed report that included pregnancy drug exposure cases necessary for close monitoring, types and characteristics of data on pregnancy drug exposure, the requirements of registry data, and essential items needed to be researched. Conclusions: Information on pregnancy drug exposure in Korea can be effectively collected by using this report which provides a comprehensive assess to drug’s influence on pregnant women and fetus, and in addition, accurate information about safety and effectiveness of drug use in pregnant women and fetus can be obtained by sharing data globally and managing it synthetically and systematically

Objective: The purpose of this study was to identify the type and frequency of chemotherapy-related prescribing errors and assess the pharmacist intervention in preventing potential harm. Methods: This study was performed in satellite pharmacy of oncology/hematology unit in tertiary teaching hospital from April to September, 2009. All chemotherapy prescribing errors detected by pharmacists were recorded. Frequency and characteristics of prescribing errors were analyzed. Pharmacists reviewed 28, 495 chemotherapy orders from 12,719 patients during 6-month periods. Results: A total of 835 prescription errors (2.93%) in 734 patients (5.77%) were detected by pharmacists. Alkylating agents (37.6%) followed by antimetabolite (23.35%), and mitotic inhibitors (21.44%) were the most prevalent classes in which errors occurs. The most common types of error detected were incorrect dose (34%), incorrect solution (33%), incorrect route (9%) and omission errors (8%). Changes in chemotherapy order due to pharmacists’ intervention occurred in all error cases. Conclusion: Pharmacists’ intervention in reviewing chemotherapy and drug orders intercepted potential harm due to prescribing errors. The current study provided strategies for reduction of medication errors.

This review summarizes gender differences in pharmacokinetics, pharmacodynamics, and adverse drug reactions. Gender differences in pharmacokinetics are categorized by four major factors: absorption/bioavailability, distribution, metabolism, and elimination. There are sex-based differences in gastric emptying time, gastric alcohol dehydrogenase activity, apparent volume of distribution, α1-acid glycoprotein level, phase I (CYP) and phase II metabolizing enzymes, glomerular filtration rate, and drug transporters. This review also reports gender differences in pharmacokinetics and pharmacodynamics of cardiovascular agents, central nervous system acting agents and antiviral agents. In addition, it has been reported that females experience more adverse reactions such as coughing, tachycardia, nausea, vomiting, rash, hypersensitivity, hepatotoxicity, and metabolic disorder after taking cardiovascular, central nervous system acting and antiviral agents. Therefore, in order to provide optimal drug dosage regimens both in male and female, gender differences in pharmacokinetics, pharmacodynamics, and adverse drug reactions must be considered.

안면홍조는 폐경기 초기 많은 여성들에게 나타나는 증상이다. 정확한 원인은 밝혀지지 않았지만 혈중 에스트로겐 수 치가 낮아졌을 때 안면홍조 증상이 나타나기 때문에 에스트로겐을 기본으로 한 호르몬 요법이 수년간 안면홍조 증상 치료의 중심이었다. 그러나 호르몬 요법이 유방암, 뇌졸중 등의 발생 위험도를 증가시킨다는 연구 결과가 발표된 이 후 많은 보건의료인들은 호르몬 요법 대신 사용 가능한 다른 치료제에 관심을 보이고 있다. 본 연구는 venlafaxine 의 안면홍조 증상 치료효과에 대한 최신 지견을 얻고자, 1990년부터 2010년 7월까지 MEDLINE에 등재된 논문을 Hot flashes와 Venlafaxine이라는 MeSH terms로 검색하여 추출한 자료 중에서 대조군이 사용된 무작위 배정 및 이 중맹검 임상연구 사례만을 선별하여 임상적 유용성을 평가하였다. 현재 venlafaxine은 안면홍조 증상 치료제로 허가된 의약품은 아니지만 최근 여러 국가에서 시행된 연구들은 venlafaxine이 효과적인 안면홍조 증상 치료제일 수 있다는 결과를 보여주고 있다.

In order to investigate the antibiotic prescription pattern for upper respiratory infections (URI), the prescription sheets for outpatients from July 2008 to June 2009 were collected from 7 community pharmacies in Ulsan City, and the prescription pattern of Pediatric and ENT physicians was analyzed. The antibiotic prescription rates of Pediatric and ENT physicians were 63.8% and 61.7%, respectively. It was also observed that the oral antibiotic prescription was 95.6% in Pediatrics and 97.6% in ENT. The most favorable antibiotics by Pediatric physicians were penicillins (21.5%) penicillinclavulanate (36.4%) and cephalosporins (16.5%), macrolides (11.6%), quinolones (3.5%), and nifuroxazide (3.5%). In case of ENT, the commonly prescribed antibiotics were also penicillin-clavulanate (47.6%), cephalosporins (31.6%), macrolides (11.9%) and sulfonamide (1.3%). The antibiotic combination rate was 7.6% in Peditrics and 1.9% in ENT, among antibiotic prescriptions. The combination of more than two oral antibiotics was examined as 66.8% in Pediatrics and 44.2% in ENT. The common oral antibiotic combination in Pediatrics was prescriptions of two β-lactam antibiotics (54.3%). Among them 83% was the combination of amoxicillin-clavulanate (7:1) and amoxicillin, which could be judged as antibiotic overuse. The next highly prescribed oral antibiotic combination was β-lactam/macrolide antibiotic combination probably for URI (11.3%) and β-lactam/nifuroxazide combination (10.0%) presumably for acute diarrhea. Comparatively the oral antibiotic combination prescribed by ENT physicians was negligible except one physician. In conclusion, the antibiotic over-prescription rate by antibiotic combination was much higher in Pediatrics than ENT, even though both clinical departments showed nealy the similar antibiotic prescription rates.

Therapeutic drug monitoring of Mycophenolate mofetil(MMF) has been suggested in some clinical trials, but has not been widely adopted in Korea. The purpose of this study was to analyze the withdrawal rates of MMF and determine the characteristics of the patients who experienced adverse reactions with MMF therapy and to suggest the criteria for selecting patients who need monitoring of MMF levels. We retrospectively collected data of patients who started MMF between July 2007 and June 2008. A total of 154 adult patients were included in our study. Among them, ninety seven patients discontinued MMF with 59 cases being due to adverse drug reactions. Thirty one patients required dosage reduction of MMF with twenty three cases being due to adverse reactions. Twenty six patients continued the MMF without or with mild adverse reactions. Of the 82 adverse reaction cases, hematologic adverse reactions accounted for 38 cases (46%) and gastrointestinal (GI) adverse reactions accounted for 28 cases (34%). Older age and lower serum albumin levels were significantly different characteristics between the patients who withdraw MMF due to hematological adverse reactions and those who were able to continue therapy. The group who experienced GI adverse reactions had higher MMF dosages based on body weight and lower serum albumin levels. In conclusion, the factors affecting the adverse reactions of MMF were age, serum albumin level and higher dosage, therefore therapeutic drug monitoring of MMF should be considered in these patients.

Radiofrequency ablation (RA) is being used to manage atrial fibrillation (AF) with patients failed at the 1st-line anti-arrhythmic medications. Patients undergoing this procedure are at increased risk of thromboembolism after ablation, and anticoagulation management surrounding the ablation remains controversial. Although no conclusive recommendations can be made, published guidelines and data support therapeutic anticoagulation with warfarin. The purpose of this study was to analyze effectiveness of current therapy and to find factors fluctuate International Normalized Ratio (INR) values in patients undergone RA followed by anticoagulation service (ACS). Retrospective review was conducted utilizing database in a hospital. Among 110 patients under warfarin around ablation between January 2006 to September 2007, 54 patients were selected and allocated into 2 groups: Group A included 47 who discontinued warfarin after ablation, while 7 in B continued the medication. Information on demographics, amount and length of warfarin dosing, INR values and measuring frequencies, and the causing factors on INR fluctuation were abstracted. Differences were analyzed using chi-squared test, Fisher's Exact test, and unpaired Student t-test. Mean amount of warfarin before and after surgery was 4.0 mg, 4.1 mg in Group A and was 5.1 mg, 4.6 mg in Group B, respectively. Average duration of warfarin doing before ablation was 73.7 days in Group A, 129.9 days in B with no significant difference (p = 0.312). The duration time of warfarin on groups after ablation lasted several months. The number of checking INRs was 4.1 and 7.6, respectively. Inter-individual variability of INR fluctuations were 2.1 ± 0.6 in Group A and 2.2 ± 0.7 in B which were not significantly different (p = 0.062). 164 cases of decreased INR were: ‘omission in taking medication, stressfulness and headache, ‘increased intake of high vitamin K foods’, ‘lifestyle change of increased physical activities’, and ‘increase of food-intakes’. To the contrary, 36 cases of increased INR were: ‘reduce of food-intake’, ‘use of non-prescription drugs’, ‘reduction in physical activities’, and ‘excessive restriction on food-intake’, consecutively. In conclusion, the study validated therapeutic outcomes of RA patients who we treated with standard guideline and demonstrated 9 factors of INR fluctuations in the patient. A well-trained, pharmacist-monitored anticoagulation service could reduce the risk of adverse effects and prevent complications in patients with AF around RA operation