약학대학에서 문제중심학습법의 효과 분석 : 충남대학교 약학대학 사례를 중심으로

윤휘열,김정태,유영훈,백현문,송병정,권광일 충남대학교 약학대학 의약품개발연구소 2016 藥學論文集 Vol.31 No.-

After exchanging pharmacy edcuation system from 4th years to 6th years at 2011, Problem Based Learning (PBL), expecially fields of pharmacotherapy, is considered as alternative teaching implements to enhance student’s skills about solving-problem, critical thinking, clinical reasoning and self-motivated learning. The purpose of this study is to analyze the effectiveness about PBL class in clinical pharmacy students, and provide the evidence of its application. Four groups consisted of 10~12 students on each (Total number of students were 54) had PBL class with 4 pharmacists who were pre-educated about PBL class as tutors. After PBL class, all of students took part in the paper-based survey about effect of PBL class in clinical pharmacy education. In results of survey, the effectiveness of PBL was superior in comparisons with traditional teaching method and student’s attitudes for class such as satisfaction and participation were also improvements. In conclusions, PBL methods had a lots of benefits about improvement of academic performance and professional knowledges in clinical pharmacy teaching, therefore PBL class should be suggested more frequently in clinical pharmacy.

식단에 따르는 페노피브레이트 서방성 캡슐의 1회 경구 투여 후 약물동태학 및 약물동력학의 평가

윤휘열,김정현,이은주,정수연,최선옥,김형기,권준택,강원구,권광일 한국임상약학회 2005 한국임상약학회지 Vol.15 No.1

We examined the effects of food on pharmacokinetic and pharmacodynamic properties of fenofibrate released from sustained-release(SR) capsule as therapy for hypolipidemia. Twenty-four healthy volunteers were used in crossover pharmacokinetic and pharmacodynamic study; Additional six volunteers were used as a control group (i.e., no fenofibrate administration). A single dose of fenofibrate (SR capsule, 250 mg) was administered on three occasions: after overnight fasting, after consumption of a standard breakfast, and after a high-fat breakfast. Serial blood samples were collected for the next 72 hours. Plasma fenofibric acid concentrations were measured by high performance liquid chromatography, and pharmacokinetic parameters were calculated using ADAPT II program. Plsama triglyceride concentrations were measured by blood chemistry analyzer (CH-100). The pharmacokinetic parameters were significantly affected by food intake. The high-fat breakfast affected the rate of absorption of fenofibrate more than did the standard breakfast and fasted conditions. Plasma concentrations of triglyceride at 24 hours decreased significantly after the administration of fenofibrate compared with the concentration at 0 hours(P<0.05). In healthy volunteers, the bioavailability of fenofibrate was greater when administered via sustained-release capsules immediately after the consumption of food than after fasting condition.

완전 모형 추정법을 이용한 임상적으로 유의한 공변량 평가

윤휘열 충남대학교 약학대학 의약품개발연구소 2014 藥學論文集 Vol.29 No.-

Adding covariates to model parameter using stepwise method are able to lead to covariate selection bias. Full model approach, which was allowing all relationships between parameters and covariates, were developed recently for improvement of selection bias. The main objective of this study was to evaluate covariates effect focused on clinical aspects using full model approach. A semi-mechanistic myelosuppression model with four structural parameters and a dataset containing 636 individuals and 3549 observations was used. The performance was evaluated in terms of model estimates and precision of parameters and ability to identify clinically relevant covariates. FOCE-I with NONMEM 7.2 assisted by PsN was used. Full model approach were successfully implemented, also good agreement in comparison with previous stepwise study, were found to be identified the same parameter-covariate relationships to be clinically relevant. Although full model approach and stepwise study performed equally well for finding covariates, however, full model approach has advantages in comparison with traditional methods when investigating clinically relevant covariates and minimize for statistical error.

소화관에서의 약물 흡수에 대한 음식물의 영향

윤휘열,백민선,권광일 한국임상약학회 2006 한국임상약학회지 Vol.16 No.2

Drugs are often taken together with meals and there are numerous opportunity for food-drug interaction to occure. Food-drug interactions and their clinical consequences are very complex indeed. The composition of the meal, and the volume of fluid that is ingested often are decisive factors in food-drug interactions. Various formulations of a specific drug may behave differently. Solutions and suspensions seem to be less susceptible and enteric-coated preparations are more susceptible, to food interactions than are other dosage forms but exceptions to this rule do exist. Furthermore, generic and environmental factors, disease and other drugs cause considerable inter- and intraindividual variation in food-drug interactions. Also, eating habits are dissimilar in different parts of the world, and diets often vary greatly from day to day. The taking of drugs together with meals offers some obvious benefits. It may help to reduce gastrointestinal irritation and compliance is improved. On the other hand, in some cases food interferes seriously with drug absorption. The purpose of this review is to clarify the complexity of food-drug interactions, and to discuss interactions that may be of clinical importance.

모델 기반학적 신약개발에서 약동/약력학 모델링 및 시뮬레이션의 역할

윤휘열,백인환,서정원,권광일,배경진,이만형,강원구 한국임상약학회 2008 한국임상약학회지 Vol.18 No.2

In the recent, pharmacokinetic(PK)/pharmacodynamic(PD) modeling has appeared as a critical path tools in new drugdevelopment to optimize drug efficacy and safety. PK/PD modeling is the mathematical approaches of the relationshipsbetween PK and PD. This approach in new drug development can be estimated inaccessible PK and PD parameters,evaluated competing hypothesis, and predicted the response under new conditions. Additionally, PK/PD modeling pro-vides the information about systemic conditions for understanding the pharmacology and biology. These advantages ofPK/PD model development are to provide the early decision-making information in new drug development process, andto improve the prediction power for the success of clinical trials. The purpose of this review article is to summarize thePK/PD modeling process, and to provide the theoretical and practical information about widely used PK/PD models.This review also provides model schemes and the differential equations for the development of PK/PD model.

조코 정에 대한 엘바스타 정의 생물학적 동등성 평가

윤휘열,강원구,권광일 한국임상약학회 2005 한국임상약학회지 Vol.15 No.1

심바스타틴은 cholesterol 생합성 과정에서 속도 조절 효소인 HMG-CoA reductase의 강력한 상경적 길항약으로서 고지혈증 치료에 널리 쓰이는 약물이다. 심바스타틴 제제인 MSD 사의 조코 20 mg정을 대조약으로 하여 시험약인 유영 제약의 엘바스타 20mg정의 생물학적 동등성 평가를 하기 위해 22명의 건강한 지원자를 모집하였다. 지원자를 두 군으로 나누어 2정씩 투여하였고 교차시험을 실시하였다. 심바스타틴의 혈장 중의 농도를 정량하기 위하여 발리데이션된 LC/MS/MS를 사용하였다. 채혈 시간은 투약 전 및 투약 후 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12 시간에 걸쳐 총 12시점에 걸쳐 시행하였다. 생물학적 동등성을 판정하기 위한 파라미터로 12시간까지의 혈장 중 농도곡선 하 면적 ()과 최고 혈중 농도()를 사용하였다. 12시간 까지의 혈중 농도 곡선 하 면적의 기하 평균은 (시험약)과 (대조약)으로 나타났다. 최고 혈중 농도의 경우 각 각 5.08 ng/ml(시험약)과 5.20 ng/ml(대조약)으로 관찰 되었다. 의 경우 로그변환한 평균치 차의 신뢰구간이 log0.8510 - log1.1694이었고, 의 경우 log0.8176 - log1.1649로 계산되어 두 항목 모두 log0.8-log1.25이어야 한다는 식품의약품 안전청과 FDA의 기준을 모두 만족시켰다. 이상의 결과를 종합하면 시험약 엘바스타 정 20mg은 대조약 조코정 20 mg에 대하여 생물학적 동등한 것으로 판정되었다.

실제 임상 데이터를 이용한 NONMEM 7.2에 도입된 추정법 비교 연구

윤휘열,채정우,권광일 한국임상약학회 2013 한국임상약학회지 Vol.23 No.2

이미그란 정 50 mg에 대한 수마트란 정의 생물학적 동등성 평가

윤휘열,백인환,권광일 한국임상약학회 2005 한국임상약학회지 Vol.15 No.2

수마트립탄은 뇌혈관에 분포되어 있는 5-HT1B/1D수용체에 특이적이고 선택적으로 작용하여 뇌혈관 수축 작용을 나타내어 편두통의 치료에 널리 쓰이는 약물이다. 본 연구는 수마트립탄 제제인 이미그란(50 mg tablet, GSK사)을 대조약으로 하여 시험약인 명인 제약의 수마트란 50mg정의 생물학적 동등성 평가를 하기 위해 22명의 건강한 지원자를 모집하였다. 지원자를 두 군으로 나누어 1정씩 투여하였고 교차시험을 실시하였다. 수마트립탄의 혈장 중의 농도를 정량하기 위하여 발리데이션된 HPLC/FD를 사용하였다. 채혈 시간은 투약 전 및 투약 후 0.5, 1, 1.5, 2, 2.5, 3,4, 5, 7, 9, 12시간에 걸쳐 총 12시점에 걸쳐 시행하였다. 생물학적 동등성을 판정하기 위한 파라미터로 12시간까지의 혈장 중 농도 곡선 하 면적 최고 혈중 농도를 사용하였다. 의 평균은 (시험약)과 (대조약)으로 나타났다. 의 경우 각 각 29.30 ng/ml(시험약)과 29.25ng/m1(대조약)으로 관찰되었다. 의 경우 로그변환 한 평균치 차의 90% 신뢰구간이 log0.95-log1.24이었고, 의 경우 log0.90-log1.149로 계산되 어 두 항목 모두 log0.8-log1.25이어야 한다는 식품의 약품 안전청 과 FDA의 기준을 모두 만족시켰다. 이상의 결과를 종합하면 시험약 수마트란 정 50 mg은 대조약 이미그란 정 50 mg에 대하여 생물학적으로 동등한 것으로 판정되었다.

프렉탈 개념을 바탕으로 한 새로운 약물동태 모델의 제시

윤휘열 충남대학교 약학대학 의약품개발연구소 2015 藥學論文集 Vol.30 No.-

당뇨병 치료를 위한 SGLT2 억제제의 심혈관계 안전성 관련 최근 임상시험 결과고찰

김혜럼, 한나영, 유미선, 권광일, 윤휘열 충남대학교 약학대학 의약품개발연구소 2017 藥學論文集 Vol.32 No.-

Patients with type 2 diabetes have a two-to three-times greater risk of developing car-diovascular disease than people without diabetes, and the mortality rate from cardiovascular disease is also reported to increase. The reason why cardiovascular disease is more common in type 2 diabetic patients is not only that cardiovascular risk factors are more common than non-diabetic patients, but also that diabetes itself is an independent risk factor for cardiovascular disease. Since rosiglitazone. which was introduced as a treatment for type 2 diabetes in 2000, has been argued to increase cardiovascular disease sluch as myocardial infarction. there were clinical trials of cardiovascular safety of it such as DREAM. ADOPT and RECORD. As a result. rosiglitazone has been banned due to the risk of cardiovascular disease. The US FDA and other regulatory agencies have required clinical trials for type 2 diabetes treatments afterward. 1n this study. it is reviewed that recently developed SGL T2 inhibitors has cardiovascular benefits as a novel mechanism of type 2 diabetes treatment. SGL T2 inhibitors inhibit the renal sodium glucose co-transporter(SGLT2), thereby reducing glucose reabsorption and increasing excretion of it. and consequently lowering blood glucose levels. Recent papers on ongoing cardiovascular-related clinical trials of SGL T2 in-hibitors such as CANVAS. CANVAS-R. CREDENCE of canagliflozin, DECLARE-TIMI 58 of dapagliflozin. and EMPA -REG outcomes of empagliflozin were examined thoroughly as well.