Background : Economic evaluation is a tool to aid the decision-making for efficient resource allocation. As recently it was proposed that cost-effectiveness should be one of important criteria on the decision for the reimbursement and pricing of drugs, economic evaluation attracted a lot of interests in Korea. Efficient resource allocation will also become a critical health policy issue in Korea because of increasing health expenditure and limited health care resources. Results : Now is the tim: for us to learn some lessons from advanced countries, particularly European countries. European countries have developed their own unique health care system and different approaches for pharmaceutical economic evaluation. We reviewed the general trends of economic evaluation of drugs, and compared several approaches in European countries. Pharmaceutical economic evaluation has been developed as not only a part of medical technology assessments, but also that of pharmaceutical policies. More and more European countries used cost-effectiveness as one of important criteria for the reimbursement and pricing decision about drugs. Even though there were variations in contribution of economic evaluation to reimbursement and pricing decision, and standard guidelines for economic evaluation from country to country, a tendency that pharmaceutical economic evaluation became mandatory was noticed. Conclusions : From the experiences of European countries, we can learn some lessons. The interests and commitment of decision makers are crucial to introduce pharmaceutical economic evaluation and to develop its infrastructure. Transparency of researches and independency from sponsor will be important issues. The criteria and decision process for reimbursement and pricing should be more specific and specialized to improve efficient decision making.

Cancer chemotherapy shows nonspecificity, narrow therapeutic indices, severe toxicity, unpredictable efficacy, and heterogeneity in their therapeutic and toxic responses across patient populations. Pharmacogenomics endeavors to elucidate the effect of genetic inheritance on the individual variation of drug response and toxicity. Many genetic factors such as genetic polymorphism in drug metabolism enzymes, drug targets, drug transporters and etc. are much responsible for variable responses and tolerability of cancer chemotherapy. Pharmacogenomics has therefore great potential to improve cancer treatment outcomes by either reducing toxicity or increasing efficacy, with its ultimate goal of realizing individualized optimal cancer chemotherapy or tailored drug therapy based upon the genetic profiles of each individual in clinical filed. Clinically relevant pharmacogenomic examples of anti-cancer drugs in their metabolism, transporters and targets are discussed. Other topics briefly discussed also in this article include the role of pharmacogenomics in the development of new anti-cancer drugs, ethical issues raised in pharmacogenomic studies, and educational needs of pharmacogenomics-related knowledge in the undergraduate, postgraduate, and continuing medical education courses.

The need and importance of clinical pharmacology education has in recent become enormous because of many reasons; 1) increasing demand of optimal drug therapy, one of major themes of clinical pharmacology, which aims to maximize therapeutic effects and to minimize adverse drug reactions, and also to reduce the cost in this process 2) explosive increase in the knowledge of currently-using drugs' clinical pharmacology and of therapeutic medicine technology, 3) increasing requirement of rational prescribing and reducing medication errors, 4) improving new drug development, 5) introduction of new pharmacotherapeutic knowledge using up-to-date techniques such as pharmacogenomics, etc., 6) the need of cultivating the ability to understand, evaluate, and to execute not only the current drug therapy but also the future drug therapy. The present status of clinical pharmacology education in Korean undergraduate courses was in this article discussed based upon the survey carried out lately in Korean medical schools and its improving measures were also described briefly. According to the survey, only about one fourth of responding medical schools had a separate or independent subject for clinical pharmacology education, with average teaching time of 13.5 hours, which is less than half of 28 hours for the average education time of clinical pharmacology in European medical schools surveyed already 14 years ago by WHO. The majority of clinical pharmacology education in Korean medical schools were done as a part of pharmacology subject with average education time of only 6.4 hours. Only 30% of the medical schools which had independent clinical pharmacology course had their own clinical pharmacologists. Other present properties of clinical pharmacology education and the problems in its education were also described. The current situation of clinical pharmacology education in Korean undergraduate courses has been shown to be severely lacking despite the need and importance of clinical pharmacology. Therefore, the teaching of clinical pharmacology in Korean undergraduate courses has to be increased a lot than now. The training of clinical pharmacologists is also urgently required. Other measures to encourage the education of clinical pharmacology in Korean undergraduate courses were also discussed.

국내 임상약리학 교육 실태조사에 의하면 국내 의과대학 교육에 있어서 치료의 중추적인 부분인 약물요법의 원칙과 술기에 대한 교육은 매우 미진한 상태로 이는 곧 의과대학을 졸업하고 진료 일선에 나가 직접 진단과 처방을 수행해야 할 의사들의 질적인 문제를 야기할 수 밖에 없다. 또한 최근 들어 bench-to-bedside (translational) research의 중요성이 대두되고 있는 현실에서는 새로운 약물 개발에 필요한 임상시험 및 이와 관련된 연구가 필수적이다. 그러나 이러한 분야에 대한 전문성을 갖춘 의사들의 수는 너무 적어 국내외 신약개발 및 임상시험 관련 산업에 큰 발전 저해 요소로 작용하고 있다. 따라서 시급히 이에 대한 대책이 논의되어야 하며, 빠른 시일 내에 이를 해결할 수 있도록 노력해야 한다. 우선 기본적으로 적절한 약물요법에 필요한 원칙 및 술기에 대한 교육이 필요하다. 기존의 약물처방에 대한 교육은 의과대학 초기학년에 주로 약물의 작용기전 및 약동학적 성질에 대한 일반적인 내용을 강의를 통해 배우나 실제 환자 진료에 있어서 이를 적용하는 데는 전혀 훈련이 되어 있지 못하다. 주로 의과대학 3, 4학년에 임상 실습시 인턴, 레지던트 또는 교수들로부터 간접적인 방법을 통해 배우기는 하나 이는 자신의 판단을 통한 처방이 아닌 단순히 흉내를 내는 정도에 그치고 만다. 이에 대한 근본적인 원인은 의과대학 교육과정 중 기존의 기초 및 임상과로부터 임상약리학 및 약물치료에 대한 수업시간을 할애 받지 못하는 적절한 시간 배정을 받지 못하는데 있다. 또한 졸업 후에도 임상약리학 분야에 대한 인식 부족 및 장래성에 대한 두려움, 지원의 부재 등으로 인해 전문가 양성에도 실패하고 있다. 현재 필요한 것은 우선 의과대학 학생교육에 있어서 약물의 안전하고 효과적인 사용에 필요한 임상약리학적 원친과 바르게 증가되고 있는 신약 및 기존 약물에 대한 정보를 습득하는 것은 물론 이들을 실제 치료에 적용할 때 약물의 평가 및 선택에 필요한 비판적인 사고를 기러주는 것이다. 또한 졸업 후에는 이들을 교육할 수 있는 임상약리학자, 신약개발 및 평가 전문가, 약물역학, 의학통계학, 약물경제학, 약물유전체학 등의 전문가 양성이 시급하며, 일선 진료에 임하는 의사들에게는 재교육을 통해 Good Prescribing Practice를 지속적으로 가르쳐야 한다. 최근 의과대학 교육과정의 변화를 보면 구미 선진국에서는 이미 전통적인 강의 형식, 정보 위주의 주입식 교육 및 과별, 특히 기초와 임상을 구분하는 교육을 탈피하고, 점차 system-based learning, 술기와 태도에 대해 초점을 맞추고 Problem-based learning으로 전환되었다. 그러나 이로 인해 임상 약리학에 필요한 내용에 대한 교육의 누락이 문제적으로 제시되고 있으며, 이에 따라 safe/effective prescribing 및 신약개발에 대한 정보 수집/평가 능력에 대한 부분을 보완하는 시도가 이루어지고 있다. 국내에서도 교육방식의 변화를 꾀하고 있으며, 이미 여러 학교에서 시도되고 있으나 아직 미완의 단계에 있다. 그러나 지금이 우리에게는 오히려 이미 선진국에서의 경험을 바탕으로 문제가 되는 부분을 새 교육과정 도입 초기부터 해결하여 똑같은 실패를 반복하는 것을 사전에 막을 수 있는 좋은 기회이다. 현재 임상약리학 교육을 기존의 시스템에 접목시키는 데는 어려움이 많다. 따라서 새로운 교육과 정의 도입으로 인해 과별 경계가 점차 없어지는 추세와 맞물려서 ‘임상약리학과’라는 독립된 과목을 고집하기 보다는 약물요법을 필요로 하는 모든 분야에 있어 실질적인 도움 및 필요성을 강조하여 자연스럽게 섞여 들어가는 방안을 제시해 볼 수 있다. 즉, 임상약리학을 Basics of Pharmacology, Adverse drug reaction, Drug interactions, Clinical toxicology, Regulations affecting prescribing, Clinical pharmacokinetics, Monitoring drug therapy, Pharmacogenetics, New drug development, Drug administration, Rational drug therapy, Drug information, Communication, skills, Writing prescriptions and record keeping, Prescribing for special groups (e.g., the elderly, children, patients with kidney or liver disease), Therapeutic drug monitoring, Patient adherence to therapy, Use of evidence, The process of optimal therapeutics, Learning for the future, The prescription as an experiment 등으로 분자화하여 질환별, 시스템별 교육과정을 흡스되도록 하는 것이다. 구체적으로는 의과대학 초기학년에 임상약리학에 대한 원칙을 간단히 교육시키녀, 차츰 질환 및 시스템과 연관된 교육 과정에 필수약물에 대한 교육을 혼합시키고, 임상실습 시 Good prescribing practice (personal drug)에 대한 코스를 가미하여 처방에 대한 실제적인 훈련을 시킬 수 있다. 졸업 후에는 임상약리학 대학원 코스를 설치하고, 임상약리학의 원칙에 대한 보수교육, fellowship 프로그램 등을 통한 전문의 제도 확립, 신약개발 및 임상시험 관련 교육/훈련 프로그램 신설 등을 통해 임상약리학 분야의 전문가를 양성해야 한다. 이를 위해서는 각 의과대학의 학장, 의학교육학회, 임상약리학회, 교육부와 보건복지부 뿐만 아니라 제약산업계의 총체적인 협조가 요구된다. 국내의 현실을 바라볼 때 이러한 일들은 시급히 이루어져야 하며 이를 위한 적극적인 지원을 해야 한다.

Background & Objectives : Macrolide antibiotics have been reported to cause several drug interactions with co-administered drugs clinically. However, there is no clear demonstration to reveal the relative potential to cause drug interaction. Therefore we investigated and compared the inhibitory effects of macrolide antibiotics on cytochrome P45C3A4 (CYP3A4)-catalyzed reactions using human liver microsomes. Methods : Macrolide antibiotics including azithromycin, clarithromycin, dirithromycin, erythromycin, and troleandomycin was co-incubated with midazolam or testosterone, probe substrates of CYP3A4, in human liver microsomes, respectively. Metabolic activities of midazolam I-hydroxylation and testosterone $6{\beta}-hydroxylation$ were determined using high-performance liquid chromatography and inhibitory effects of macrolide antibiotics were determined by the calculation of $IC_{50}$ (the concentration of inhibitor representing 50% inhibitory potency) values by nonlinear regression method. Results : Among macrolide antibiotics tested, troleandomycin inhibited midazolam 1-hydroxylation and testosterone $6{\beta}-hydroxylation$ potently with $IC_{50}$ values of 52.3 and $65.9{\mu}M$, respectively. Clarithromycin and erythromycin showed moderate and similar inhibitory potency on both CYP3A4-catalyzed reactions. However, azithromycin and dirithromycin showed little inhibitory effects on CYP3A4-catalyzed midazolam 1-hydroxylation and testosterone $6{\beta}-hydroxylation$. Conclusions : Dirithromycin and azithromycin showed little inhibitory effects on CYP3A4-catalyzed reactions. However, other macrolide antibiotics including troleandomycin, clarithromycin, and erythromycin caused significant inhibitory effects, thereby it should be cautious to co-medicated these drugs with other CYP3A4 substrates that have a narrow therapeutic range or concentration-dependent toxicity.

The role of ethics committees or institutional review boards (IRB) is crucial to ensure the scientific and ethical quality of medical research involving human participants. In April 2002, the Korean Association of Institutional Review Boards (KAIRB) conducted a survey to examine the current constitution and operation of IRBs in Korea. Out of 74 IRBs, 63 responded to the survey (85.1% response rate). The survey analysis shows that the number of the IRBs has abruptly increased since 1995, when the KGCP (Korean Good Clinical Practice), the regulation for clinical trials, began to be enforced. The survey shows that IRB membership has a male: female ratio of approximately 80:20, a predominance of male clinicians (60 %) and a lack of community representatives unaffiliated to the institution (less than 10 %). Most IRBs (80%) confine the scope of their review to the clinical evaluation of drugs or devices, leaving the remaining areas of research involving human participants untouched. As their role is limited, the majority of IRBs do not operate actively: 72 % of responding IRBs reviewed less than one protocol per month in 2001. Many IRBs lack detailed standard operating procedures. While 70% of the IRBs review payment and compensation to patient participants and healthy volunteers in sponsored research, 62% of institutions have never discussed the need for insuring research participants risks or making indemnity arrangements. This survey on the current situation of IRBs in Korea reveals many shortcomings and points for improvement by the institutional support bodies, including the need to establish regular education programs for IRB members and investigators.

Purpose : This study was aimed to evaluate the current status and to establish the infrastructure for clinical trial in the aspects of manpower, facilities, IRB, SOP in Korea. Method : This was used survey, literature review, visiting to developed country, discussions with the professionals in seminars and workshop. Result : The number of professional member was less than that of the developed countries, and there's no systematic educational programs. Second, there's little space only for clinical trial as well as national standards is unsatisfactory. Third, the scope of IRBs review were limited, and the educational programs of IRB members and investigators were inappropriate. Fourth, the investigators site SOPs were not standardized, and the adherences to SOPs were questionable. Conclusion : For manpower, educational programs and revision of KGCP is needed. For facilities, the standard for the clinical trial facilities should be made and be used as accreditation index of institution. For IRBs, both the scope of IRB review and training programs for IRB members should be expanded, and the quality control system of them should also be introduced. For investigator site SOP, it should be inserted into the KGCP, and SOP training programs should be developed.

Background: Korea has very high prevalence of penicillin- and macrolide-resistant Streptococcus pneumoniae in the world. The impact of such resistance has not been measured properly. This study tried to estimate the clinical outcome of initial treatment according to the choice of antibiotics in outpatient treatment of community-acquired pneumonia(CAP) caused by S. pneumoniae in South Korea. Methods : We employed the probabilistic model to calculate rates of initial treatment success and hospitalization for CAP in adult without major co-morbidities. Three 2-step strategies were considered: Initial treatment with (1) clarithromycin, (2) amoxicillin-clavulanate, or (3) telithromycin; and failures of initial treatment were treated with levofloxacin. We used surveillance data from the 1999-2000 PROTEKT study, and applied the proportions of susceptible organism to each antibiotics to calculate the failure rates. We assumed spontaneous resolution of 10% regardless of treatment strategy and treatment success of 90% if organisms were susceptible to the chosen antibiotics. We also assumed that 20% of initial treatment failures would be hospitalized, the others given a second prescription. All patients failing the second round of therapy were assumed to be hospitalized. Results : According to PROTEKT Korea, resistance of S. pneumoniae isolates to clarithromycin, amoxicillin-clavulanate, levofloxacin and telithromycin was 87.6 %, 30%, 3%, and 0%, respectively. The model calculated initial treatment success to be 15.6% for clarithromycin, 64.9% for amoxicillin-clavulanate and 90.5% for telithromycin. The hospitalization rate was 25.4% for clarithromycin/levofloxacin, 10.6 % for amoxicillin-clavulanate/levofloxacin, and 2.9% for telithromycin/levofloxacin. Results for telithromycin were not sensitive to breakpoint (range 0.5-4.0 mg/L). Conclusion : The modeling suggests that initial treatment with telithromycin --- the first ketolide antibacterial --- has the potential to increase the success of initial treatment to 90.5% comparing with clarithromycin(15.6%) and amoxicillin-clavulanate(64.9%) in out-patient with S. pneumoniae CAP in South Korea. It also reduce the percentage of hospitalization to 2.62% comparing with clarithromycin(73.85%) and amoxicillin-clavulanate(16.87%).

Background: This is postmarketting surveillance to evaluate the efficacy and safety of tramadol/acetaminophen in patients with painful musculoskeletal diseases. Methods : A total of 890 patients (male 157, female 733) were included in the department of rheumatology at 24 hospitals from January, 2003 to November, 2003 who had taken tramadol/acetaminophen at least 2 weeks to manage the pain. Outcome measure was pain relief examined through numeric rating scale (NRS), and adverse events were monitored. We analyzed the relation between adverse events development and age, sex diagnosis, combined analgesics or NSAIDs, and drug dose by multiple logistic regression method. Results : Patients with osteoarthritis (69.1%), rheumatoid arthritis (17.1%), fibromyalgia syndrome (2.8%), ankylosing spondylitis (1.0%), systemic lupus erythematosus (0.7%), Behcet's disease (0.7%), and other diseases were included in order. Pain examined by NRS was significantly lowered after use of tramadol/acetaminophen medication; before $6.58{\pm}1.45$, after $4.17{\pm}1.78$ ($p=2.15{\times}10^{-22}$). This effect on pain relief was apparent in subgroups with moderate (NRS 4-6) and severe (NRS 7-10) pain before use of tramadol/acetaminophen, but not in subgroup with mild (NRS $1{\sim}3$) pain. The adverse events occurred in 75 patients (8.4%), and were nausea (32), vomiting (18), dizziness (15), abdominal discomfort (10), dyspepsia (6), anorexia (6), malaise (5), constipation (4), and micturition disorder (3) in order. Only age was associated with the development of adverse events in multiple logistic regression analysis. Conclusions : Tramadol/acetaminophen effectively managed pain in various musculoskeletal diseases, especially in patients with moderate to severe painful condition, and no other adverse event was reported except those listed in insert paper.

UDP-glucuronosyl transferases (UGT) mediate a conjugation reaction by glucuronidation of various clinically important drugs. The functional significance of genetic polymorphisms in these UGTs are main concern of the current researchers of UGTs. Valproate (valproic acid) is an antiepileptic drug glucuronidated mainly by UGT2B7. We investigated the effect of genetic polymorphism on pharmacokinetics of valproate in healthy normal volunteers. Before the clinical study, we screened genotype of UGT2B7-T801A (T:*1, A*2). Twenty three healthy subjects were enrolled and grouped with regard to the UGT2B7 genotype. The pharmacokinetic profile of valproate was characterized after valproate administration (600 mg once daily for 5 days). The plasma concentrations of valproate were analyzed before and I, 1.25, 1.5, 2, 2.5, 3, 5, 7, 9, 13, 25, 49 hours after $5^{th}$ valproate administration by TDX with FPIA method. Although the pharmacokinetic profiles of valproate did not. showed significant differences between the UGT2B7 genotype groups, a trend of decrease of clearance as increase of UGT2B7*2 allele was observed. Oral clearance of valproate in the UGT2B7*2/*2 group was 66% of that of the UGT2B7*1/*1 group. The results suggest that the UGT2B7*2/*2 genotype group possibly has a decreased clearance of valproate. Further study may be required to clarify the results.