Individual variation in drug response is one of major issues in clinical practice and of a drug development. These variation can range from therapeutic failure to adverse or even fatal effects of drugs in some patients. The incidence of serious and fatal adverse drug reactions (ADRs) has been reported to be 6.7% and 0.32% of hospitalized patients in USA, respectively. The risk for therapeutic failure or toxicity of a drug in an individual patient is determined by the interaction of genes and environment. Environmental factors include drug-drug interactions, patient's age, weight, renal and liver dysfunction, or other disease factors or clinical variables such as smoking and alcohol consumption. Many of these environmental factors have long been considered in determining the individualized dose regimen in conventional pharmacotherapeutics. However, inherited individual variability of drug responses has been left as a so called 'idiosyncrasy' that are not predictable by physicians. Recently, the rapid development of pharmacogenetics/pharmacogenomics provide us extensive informations regarding on the genetic background on the wide inter-individual variation of drug responses, which is expected to lead to the era of personalized pharmacotherapy. Pharmacogenetics is a science that is interesting to the inherited variants of genes related to pharmacokinetics (drug metabolizing enzymes, drug transporters etc.) and pharmacodynamics (receptor, ion channel, target enzyme etc.), which are associated to the susceptibility of an individual to the higher risk of ADR or therapeutic failure. This review addresses the role of pharmacogenetics/pharmacogenomics in relation to wide interindividual variation of drug responses and to the possible contribution to the prediction of personalized pharmacotherapy.

배경 : 최근 국내에서 생산되는 omeprazole 경구제제인 오메놀 (한국유나이티드제약)의 생체이용율을 비교 검토하기 위하여 대조약인 로섹(아스트라제약)과 생물학적 동등성시험을 실시하였다. 방법 : 20-40세되는 건강한 지원자 16명을 대상으로 라틴방격법으로 2회에 걸쳐 omeprazole 20 mg을 무작위 교차투여 하였다. 약물투여 전 및 투여 후 12시간까지 총 9 회 채혈하여 혈장 내 omeprazole 농도를 HPLC로 분석하였다. 결과 : 생체이용율의 지표로 대조약 로섹과 시험약 오메놀의 곡선하농도(AUC), 최고혈중농도(Cmax) 및 최고혈중농도 도달시간(Tmax)을 분산분석한 바 대조약과 시험약사이에 유의한 차이가 없었으며 각각의 평균치 차이는 각각 8.05%, 2.49%, 3.17%로서 모두 20% 이내 이었다. 또한 시험약의 AUC, Cmax, 및 Tmax의 신뢰한계는 동등성 기준을 만족시켰다. 결론 : 이상의 결과로 보아 시험약 오메놀은 기준약 로섹과 비교하여 생물학적으로 동등하다고 인정된다.

Background : The discipline of clinical pharmacology has been trying to improve the efficacy and safety of drug therapy on a scientific basis, and also to attain rational prescription. Clinical pharmacology has also played the vital role in new drug development. It is clear that medical students should receive a sound education in clinical pharmacology during their undergraduate course so that they can easily understand current therapies as well as evaluate and assimilate new therapeutic advances in the future. The current status of clinical pharmacology education in Korean medical schools was therefore investigated. Method : A nation-wide survey on the current status of clinical pharmacology education were conducted in 41 Korean medical schools. Results : 38 (92.7%) schools responded to the questionaire on the current status of clinical pharmacology education. Only about one fourth (26.3%) of respondents were teaching clinical pharmacology as a separate discipline. In case of separate clinical pharmacology course, an average time of clinical pharmacology education was 13.5 hours and the education was done most frequently during the 4th-year grade of medical curriculum. The main subjects taught most frequently were clinical pharmacokinetics, therapeutic drug monitoring, drug use in elderly and children, drug use in kidney disease patients, etc. In case of 25 medical schools in which clinical pharmacology lecture is included as just one part of existing pharmacology course, the average time of clinical pharmacology lecture was only 6.4 hours. Fifteen schools among 28 schools (53.6%) which do not have an independent clinical pharmacology course expressed the future plan to have an independent clinical pharmacology course of average 16.9 hours. Conclusion : These data indicated that there are severe deficiency of clinical pharmacology teaching in Korean medical schools, and every effort is urgently required to encourage the education of clinical pharmacology in undergraduate medical curriculum in Korea.

Background : Measurement of blood glucose is a basic part of patient care. Increasingly, blood glucose measurement has become a part of self-care. Devices featuring convenience and quickness are used to measure blood glucose and are used in settings often unsupervised by knowledgeable health care personnel. In this context, a validation test of a handy assurances that the devices that they are using or purchasing are capable of producing valid results. Method : In this study, we fulfilled requirements from the ICH Q2 guidelines for assurance of accuracy, precision, linearity and range. From the two subjects, blood glucose was measured repeatedly at post-prandial 1h/2h/3h/4h, 12 times each, by two investigators and with two instruments. Then, we compared the results of a handy blood sugar measuring instrument with those of a chemistry analyzer, Hitachi 7070 auto-analyzer, in a core laboratory in Clinical Trial Center, Seoul National University Hospital. Results : Mean accuracy, intra-assay precision and intermediate precision were 92.6%, 2.3%(min. 1.07%, max. 4.51%), 1.73%(min. 0%, max. 5.65%) each. In scatter plot of the results of a handy blood sugar measuring instrument and Hitachi 7070 auto-analyzer, linearity was apparent and the correlation coefficient(r), $r^2$ was 0.986 and 0.972 each. Conclusions : Mean accuracy was not satisfactory regarding the criteria for quality control of blood glucose $measurement(within {\pm}5%)$ in SNUH. The intermediate precision was also not satisfactory regarding the criteria for Quality Control (less than 5%).

배경 : 간 cytochrome P450 2C19 (CYP2C19) 효소군은 유전적 다형성을 나타내는 대표적인 약물대사효소의 하나로, 본 연구에서는 다수의 한국인에서 CYP2C19 유전자 변이를 분석하고, 이들 변이 allele들의 출현빈도를 타 종족에서의 결과와 비교 분석하였다. 방법 : 282 명의 건강한 한국인 피험자에서 CYP2C19 (*2와 *3) allele 변이를 polymerase chain reaction restriction fragment length polymorphism (PCR­RFLP) 방법을 이용하여 분석하였다. 결 과 : 282명의 한국인 피험자 CYP2C19*1/*1 (41.8%), CYP2C19*1/*2 (35.5%), 및 CYP2C19*1/*3 (8.5%) allele 변이를 가지는 extensive metabolizer(EM)는 총 242명으로 나타났다. 40명 (14.2%)은 CYP2C19 의 poor metabolizer(PM)로 밝혀졌는데, 이들의 allele 빈도는 CYP2C19*2/*2, CYP2C19&2/*3, 및 CYP2C19*3/*3 가 각각 8.9%, 3.9%, 1.4% 로 나타 났다. 또한, 총 564개 allele에서 각 allele의 출현빈도는 CYP2C19*1, CYP2C19*2, 및 CYP2C19*3가 각각 63.8%, 28.6% 및 7.6%로 나타났다. 결 론 : 한국인의 CYP2C19 PM 유전형의 빈도는 중국인, 일본인 등의 동아시아인보다 다소 낮았으나, 이는 서양인에 비해서는 유의하게 높은 것으로 나타났다.

Background : Depression is quite a common disease in primary care however, studies for the safety and effectiveness of antidepressants in primary care setting are rare in Korea. Objectives : This multi-centered post-marketing study was performed to evaluate the safety and effectiveness of Moclobemide and to find out the factors related to the adherence among patients with depression in family practice. Methods : A total of 386 patients were enrolled from July 1999 to January 2000 by twenty family doctors from fifteen family practice centers. They were prescribed Moclobemide and were reevaluated at the 4th, 8th, and l2th week. Evaluation of compliance, safety and effectiveness were performed with pre-made, structured self-reported questionnaires. Evaluation of effectiveness was also performed utilizing self-rating depression scale (SDS). Results : Among 386 patients, safety was evaluated in 310 patients and effectiveness was evaluated in 239 patients. During the first 12 weeks, the number of subjects continuing with Mocclobemide was 136(37.1%). 141 subjects (38.4%) discontinued taking the drug and 90 subjects (24.5%) dropped out at the 12th week. Considering drop-out patients as ineffective cases, overall effectiveness was estimated to be 84.5%. Symptoms improved with time in patients whose follow-up were completed (P<0.01). The SDS score decreased by an average of ${6.8{\pm}9.1(12.2{\pm}19.1%)}$ after 12 weeks(p<0.01). During the study, 33(10.6%) subjects reported adverse events. The most commonly reported adverse events, in descending order, were dizziness(2.3%), headache(1.6%), insomnia(1.3%), facial edema(1.3%), constipation(1.0%), nausea(1.0%) and tremor(1.0%). The main reasons for discontinuing antidepressants were attributed to improvement of symptoms and manifestation of adverse events. Conclusion : The percentage of adherence at 12th week of Moclobemire among patients suffering from depression in the family practice outpatient clinic was shown to be 49%. The antidepressant effect and safety of Moclobemide was relatively superior.

Clinical investigations of medical devices are very important to verify its effectiveness, benefit, and safety. Therefore, preclinical trial established by ISO is essential to human clinical study. In Korea, 'clinical investigation guidelines for medical devices' was promulgated by KFDA with its applicable regulatory requirement in 2001, and clinical investigations have been supervised to be scientific and ethical. This guidelines are based on principle of biomedical and clinical research which is specified in 'Helsinki Declaration', and include duty, rights and responsibility of sponsor, IRB, inspector and subject for in scientific and ethical reasonability. Modern technology has lead to sophisticated medical devices and had much impact on medicine, but it has also produced ethical problems in the process of development Ethical problem in clinical research ranges from human to animal. However, animal experiment is essential in order to confirm that such alternative ways are comparable to animal subject. Clinical investigation is a developing stage for a future patient or human, and highest priority should be given to human rights. The training of ethical concerns to the experts who participate in development or manage medical devices is also necessary.