Earticle

항혈소판제인 티크로피딘과 항고혈압제인 니칼디핀과의 약동학적 상호작용 연구를 위하여 티크로피딘 (3 또는 10 mg/kg) 과 니칼디핀의 경구 (4 mg/kg) 및 정맥 (12 mg/kg) 투여하여 본 연구를 시행하 였다. 연구방법: 티크로피딘이 cytochrome P450 (CYP) 3A4 활성과 P-glycoprotein (P-gp)의 활성에 미치는 영향도 평가 하였다. 결 과: 티크로피딘과 니칼디핀의 병용투여 시 티크로피딘이 니칼디핀의 약물동태 파라미터에 미치는 결과는 다 음과 같다. 티크로피딘은 CYP3A4 효소의 활성을 저해 하였으나 P-gp활성에는 영향을 미치지 못하였다. 니칼디핀의 혈 중농도곡선하면적 (AUC)는 대조군에 비해 티크로피딘 10 mg/kg 병용투여군에서 유의성 (p < 0.05)있게 증가되었다. 상 대적 생체이용률 (RB)은 티크로피딘 병용 투여군에서 115-143%로 증가하였다. 결 론: 본 논문에서 흰쥐에 티크로피딘 과 니칼디핀을 병용경구투여 시 니칼디핀 의 생체이용률 (bioavailability)이 유의성 (p < 0.05)있게 증가된 것은 티크로피 딘이 대사효소인 CYP3A4를 억제하여 소장과 간장에서 초회통과효과 (first-pass metabolism)를 감소 시켰기 때문 인 것으로 사료된다. 본 실험결과를 토대로 인체에서 티크로피딘과 니칼디핀의 상호작용을 검토한 후 투여용량을 조절하 는 것이 바람직하다고 사료된다.

Background: Cefcapene pivoxil hydrochloride, is an ester-type oral cephem antibiotic. This study was performed to compare the pharmacokinetics and evaluate the bioequivalence of two cefcapene pivoxil hydrochloride 75 mg formulations. Method: In a randomized 2×2 crossover study, sixty healthy male volunteers were randomly assigned into two groups. After a single dose of 75 mg cefcapene pivoxil hydrochloride oral administration, blood samples were collected at specific time intervals from 0-12 hours. The plasma concentrations of cefcapene pivoxil hydrochloride were determined by LC-MS/MS. The pharmacokinetic parameters were determined from the plasma concentration-time profiles of both formulations. The pharmacokinetic parameters such as AUClast, AUCinf and Cmax, were calculated and the 90% confidence intervals for test/reference ratio for pharmacokinetic parameters were obtained by analysis of variance on logarithmically transformed data. Results: The mean value for AUClast in test and reference drug was 4053.1±876.5 ng·hr/mL and 3595.7±1029.1 ng·h/mL, respectively. The mean value for Cmax in test and reference drug was 1324.9±321.4 ng/mL and 1159.1±335.9 ng/mL, respectively. The 90% confidence intervals of the AUClast and Cmax ratio for test drug and reference drug were log 1.09-log1.22 and log 1.09-log1.24, respectively. No adverse events were reported by subjects or found on analysis of vital signs or laboratory tests. Conclusion: This single dose study found that the test and reference products met the regulatory criteria for bioequivalence in these health volunteers. Both formulations were safe and well tolerated in 75 mg of cefcapene pivoxil hydrochloride.

서론: 주사제 사용을 줄이기 위한 정책의 일환으로 건강보험심사평가원은 의 료기관별 주사제 처방률을 통보하고 있으 나, 여전히 주사제 처방은 높은 실정이다. 따라서 본 연구에서는 주사제에 대 한 환자의 인식수준을 살펴보고, 환자의 주사제 요청에 영향을 미치는 요인을 파악하고자 하였다. 연구방법: 본 연구는 최근 6개월 이내에 병의원을 방문한 전국의 20세 이상의 남녀를 대상으로 전화조사한 단면설계 연구다. 환자의 일반적 특성과 주사제에 대한 태도, 인식을 조사하였고, 환자 가 주사제를 요청하는데 영향을 미치는 특성을 규명하기 위해 일반적 특성(성, 연령, 결혼여부, 보험형태, 지역규모, 질환, 교육, 소득 등), 주사제에 대한 인 식, 태도를 독립변수로 하고, 주사제 처방 요청여부를 종속변수로 하며, 16개 행정지역을 무작위 효과로 층화한 다수 준 분석을 실시하였다.결과: 연구대상에 포함된 응답자는 997명이었고(응답률 82.2%), 응답자 중 24%가 병의원 방문 당시 주사제를 요구했다고 응답했고, 58%가 한번 이상 주사제를 맞은 경험이 있다고 보고했다. 92%가 주사제에 대 해 잘못된 인식을 갖고 있었고, 15%는 의사가 부적절하게 주사제를 처방한다 고 응답했다. 다수준 로지스틱 회귀분석 결과, 남성의 경우(Odds ratio(OR) 0.71, 95% confidence interval(CI) 0.52- 0.99), 고졸이상자(OR 0.63, 95% CI 0.41-0.96), 기혼자(OR 1.72, 95% CI 1.01-2.92)가 주사제를 더 요구하는 것으 로 나타났고, 대도시에 비해 농촌지역 환자가(OR 2.12, 95% CI 1.24-3.63), 호흡기계 질환으로 방문한 경우(OR 1.48, 95% CI 1.03-2.12), 주사제를 처 방하면 경구제에 비해 신뢰감이 생긴다는 응답자의 경우(OR 1.91, 95% CI 1.33-2.73) 주사제를 더 요구하는 것으 로 나타났다. 결론: 본 연구결과 여성, 기혼자, 농촌 거주자, 호흡기계 질환으로 방문한 환자 의 경우와 주사를 맞으면 신뢰감이 생 긴다는 잘못된 태도를 가진 환자가 주사제를 요구하는 것으로 나타났고, 이러 한 환자특성을 고려하여 주사제 사용을 감소시키기 위한 정책을 실시하는 것이 필요하겠다.

Modern biologics are biotechnology-derived therapeutics, including recombinant therapeutic proteins like monoclonal antibodies, cytokines and tissue growth factors. Although the pharmacokinetics of therapeutic biologics should be evaluated based on the same general principles as small molecules, careful considerations should be given to bioanalytics and pharmacokinetics when designing pharmacokinetic studies of biologics during their drug development, due to their different physicochemical properties compared with small molecules. The aim of this study was to develop a draft guidance on pharmacokinetic studies of therapeutic biologics in clinical studies. All the elements outlined in the current Food and Drug Administration (FDA), European Medicinal Agency (EMEA), and International Conference on Harmonisation (ICH) guidelines and regulations, and the related literatures previously published were searched and evaluated. In this draft guidance, the specific problems related to the pharmacokinetics of therapeutic biologics that need special consideration during drug development process were addressed, and differences in pharmacokinetic characteristics between biologics and small molecules affecting the content of the development programme were presented.

In Korea, elderly population aged 65 and older are about 5.0% and 10.7% in 1990 and 2009, respectively. Since elderly people may experience physiologic changes with aging and their pharmacodynamic and pharmcokinetic parameters also have been undergone changes, several adverse drug reactions can occur more frequently than young people. Especially, neuropsychiatric adverse drug reactions such as delirium and drowsiness endanger elderly patients more. The purpose of this study is to evaluate the outpatient prescriptions using drug causing delirium and drowsiness in elderly patients aged 65 and older. We retrospectively reviewed prescriptions for elderly patients collected from four community pharmacies from January 2nd to February 1st, 2010. One pharmacy was located closed to a general hospital, and others were located closed to a internal medicine or an ENT clinic. The each number of the collected prescriptions was followings; Group A (n=496) from internal medicine department of a general hospital; Group B (n=44) from ENT department of general hospital; Group C (n=144) from internal medicine clinic; Group D (n=110) from ENT clinic. In result, in Group A, the average number of prescribed drugs causing delirium or drowsiness per Rx was 2.38 In Group B, the average number of prescribed drugs causing delirium or drowsiness per Rx was 2.09 In Group C, the average number of prescribed drugs causing delirium or drowsiness per Rx was 2.51. In Group D, the average number of prescribed drugs causing delirium or drowsiness per Rx was 2.72. Especially, in Group D, the percentage of prescription that drugs causing delirium or drowsiness per Rx prescribed more than 3 is 52.73% In all the 4 groups, over the 60% of drugs causing delirium and/or drowsiness per prescription of elderly patients were prescribed. It means elderly patients take 2 drugs causing delirium and/or drowsiness among 3 drugs, which is very serious. Frequently prescribed drugs causing delirium and/or drowsiness were followings; GI agents, antitussives & expectorants, histamine H1 antagonist, analgesics, antibiotics. Among these drugs, GI agents was high raking in all the 4 groups, and pharmacists should caution elderly patients when counseling. In the internal medicine groups (Group A,C), drugs concerning chronic diseases were prescribed frequently. In conclusion, pharmacist's role is important. Pharmacists are well informed of the drugs causing delirium or drowsiness and it is important to explain about ADRs slowly and easily to the elderly patients that receive drugs causing delirium or drowsiness. And institutional device is needed. For example, when doctors prescribe drugs for the elderly patients, message is needed that supply some informations about drugs causing delirium or drowsiness.

Adverse drug reaction (ADR) is a global problem of major concern in health care. ADRs can be accrued in any organs or systems. However, cardiovascular ADRs could be a more serious problem if they are irreversible or severe. For this reason, this study was conducted to analyze pattern and severity of cardiovascular ADRs, and suspicious medication. Total 646 reports including cardiovascular ADRs reported to the KFDA between January and June 2010 were analyzed. Amlodipine besylate (36 reports, 3.3%), iopromide (29 reports, 2.7%), tramadol HCl (28 reports, 2.6%) were most suspicious drugs that occurred cardiovascular ADRs. The most common cardiovascular ADRs were hypotension( 236 reports, 33.1%), palpitation (134 reports, 18.8%), and hypertension (89 reports, 12.5%). The most frequent ADRs were occurred in the age group of more than 60. This result could be of help to prescribers and other healthcare providers to predict and prevent cardiovascular ADRs. Also this study suggested that patients with cardiovascular ADR risk factors should be intensively monitored during the medications

목적: 급성 상기도 감염에 사용되는 항생제 처방유형을 조사하여 항생제 사용 을 개선하는데 있다. 방법: 2011년 1월부터 6월까지 경상대학교 병원을 포함한 10개 국립대학병원 을 대상으로 급성 상기도 감염에 사용한 항생제 처방율을 조사하고, 경상대학교병원에서 급성 상기도 감염에 사용한 2011년 1월부터 6월까지의 외래환자를 대상으로 항생제 처방 내역을 전자의무기록을 통하여 후향적으로 분석한 후 처방의를 대상으로 항생제 사용 적정성 검토를 위한 그룹미팅 및 교육, 급성 상기도 감염에 항생제 처방 시 경고 안내 문을 보여주는 등 중재활동 후 2011 년 12월에 처방유형을 조사 하였다. 결과: 경상대학교병원에서 2011년 1월부터 6월까지 급성 상기도 감염에 항생 제 사용은 1739명의 상기도 감염 외래 환자 중에서 874명 (42.3%)으로 나타났다. 진료과별 급성 상기도 감염에 대한 항생제 처방은 소아과, 이비인후과, 내과, 응급의학과, 호흡기내과, 흉부외과 등에서 처방하였으며 소아과에서 1044명의 상기도 감염환자 중 556건 (53.3%)로 가장 빈번하게 사용하였으며 처방율은 이비인후과에서 58.9% (225/382)로 가장 높았다. 사용한 항생제로는 amoxicillin-clavulanic acid가 371례 (36.3%)로 가장 빈번하게 처방된 약제이 며, azithromycin이 85례 (9.7%) 처방되 었다. 급성 상기도 감염 중 급성 편도염에 항생제 처방율이 가장 높았으며 (70.8%, 80/113), 급성 인두염에 가장 빈번하게 사용되었다 (61.1%, 319/522). 균동정을 위한 혈액배양 의뢰 건수는 1739 상기도 감염 환자 중 15명 (항 생제 미사용 4명, 사용 11명)이 의뢰되었으며 모두 음성이었다. 중재활동 후 2011년 12월 상기도 감염에 항생제 처 방건수는 소아과에서 1건, 이비인후과에서 2건으로 나타났다. 결론: 처방의를 대상으로 적절한 항생제를 사용을 권장하는 지속적인 교육 및 항생제 처방시 경고 안내문을 띄우는 등의 중재활동과 지속적인 모니터링 및 피드백은 급성 상기도 감염에 있어서 항생제 처방유형에 변화를 보였다.

The quinolones are broad-spectrum antibiotics and enhanced antimicrobial activity has extended the use of the quinolones beyond the traditional indications for quinolone antibiotics in the treatment of urinary tract infections. The quinolones are effective in a wider variety of infectious diseases, including skin and respiratory infections. Because of their excellent safety and tolerability, they have become popular alternatives to penicillin and cephalosporin derivatives in the treatment of various infections. A retrospective study was performed to evaluate efficacy and safety of IV quinolones for inpatient use. Total 117 patients who administerd quinolones for longer than 3 continuous days at community hospital from October 1st, 2008 to December 31st, 2008 were reviewed. The criterias for drug evaluation were included the validation of indication, outcome, dosage and side effects. In the results, ciprofloxacin 13 (total 93), levofloxacin 3 (total 59) and moxifloxacin 2 (total 19) cases were not met the criterias based on the culture results. Major indications were pneumonia (ciprofloxacin 16.3%, levofloxacin 67.8%, moxifloxacin 84.2%), urinary tract infection (ciprofloxacin 44.1%), skin infection (ciprofloxacin 7.5%, levofloxacin 20.3%, moxifloxacin 10.5%), intra-abdominal infection (ciprofloxacin 10.8%, moxifloxacin 5.3%), etc.. In the results of quinolone monotherapy, the frequencies were each ciprofloxacin 74.2%, levofloxacin 50.8% and moxifloxacin 47.4%. In the results of dosage validation, the validities were each ciprofloxacin 54.8%, levofloxacin 94.9% and moxifloxacin 100.0%. In the results of duration validation, the validities were each ciprofloxacin 59.1%, levofloxacin 78.0% and moxifloxacin 89.5%. Adverse drug reactions were reported for total 49 cases and those were gastrointestinal tract effects including nausea, vomiting, diarrhea and central nervous system effects including headache, dizziness. In summary, the quinolones appropriately used for hospitalized patients based on this study. A focused approach emphasizing "correct use of quinolones" may reduce development of antimicrobial resistance and maximize class efficacy. Consequently, correct use of antibiotics will contribute to decrease medical expenses for person and community.

Antidepressants are frequently prescribed for a wide range of symptoms. Surveys in several countries have suggested that negative attitudes towards antidepressants are common. However, there has been limited research associated with the attitudes in Korea. Therefore, this quantitative descriptive study describing the perception and attitudes toward antidepressants was performed using healthy people and outpatients who are not taking antidepressants. The surveys by means of self-reporting questionnaires showed negative attitudes towards antidepressants (74.2%). But, 74.2% of above participants gave positive answers to take antidepressants when they are counseled by medical professionals. Higher rates of negative attitudes were found in younger age group (“it causes addiction”) and healthy volunteers and urban area groups (“it causes physical harm”). Study participants without experiences in taking antidepressants showed more negative attitudes although the difference was not statistically significant. Based on the results, accurate and objective information about antidepressants needs to be provided by well-trained health professionals.

This study was to describe inappropriate drug use in outpatient pediatrics who having 2 or more same-day prescriptions. Retrospective drug utilization reviews(DURs) were implemented to samples from national health insurance claims data during December 2008 to February 2009 nationwide, using 5 DUR criteria(duplication, drug-drug interaction, drugdisease interaction, drug-age contraindication, incorrect dosage) established in the Drug Information Framework(DIF)- Korea™ DUR program. Among 38,451 claims analyzed in the study, 74.7% had one or more conflicts in the 5 DUR modules. Among 16,472 patients analyzed, 49.6% had conflicts with duplication criteria composing ingredient duplication( 23.3%) and therapeutic class duplication(39.6%). Incorrect dosages were found in 73.6% of patients and under-dosage conflict accounted for 59.9% which is higher than over-dosage conflict (38.3%). In this study, inappropriate drug prescriptions such as under-dose, pediatric contraindication and therapeutic duplication were prevalent in pediatrics outpatient setting, suggesting much more awareness in a societal perspective, to prevent drug related problems in a vulnerable pediatric group.

This study was aimed to examine the prescribing patterns of antivirals in chronic hepatitis B(CHB)for outpatients. National Health Insurance adjudicated claims data(total 1,426,065 claims) dated March 19, 2008 submitted from nationwide healthcare providers to Health Insurance Review and Assessment Service were used in this study. 2,965 claims included CHB diagnosis(ICD-10 code B18.0 and B18.1). 44.2%(1,311) of CHD related claims included antiviral prescription such as lamivudine, clevudine, adefovir and entecavir which were currently available. Lamivudine, adefovir, clevudine and entecavir shared 54.9%, 19.9%, 13.2% and 11.9%, respectively among antiviral prescriptions. Adefovir and entecavir 1mg presumed as the 2nd line therapy for HBV resistant cases were shared 23.3% of overall antiviral prescriptions. There were statistically significant difference in prescription patterns according to age and instititution type: Lamivudine usage was higher in younger(< 20) and older age group(> 70 year old) than others(p = 0.016), and adefovir and entecavir which were relatively newer antivirals had higher prescription rate in higher level of institutions such as the 3rd level hospital than others(p < 0.001). This study would be of help to makeappropriate drug therapy plan for CHB patients.