BACKGROUND: Dutasteride is an inhibitor of both types I and II 5 alpha-reductase and was approved in Korea in April 2004. This post-marketing surveillance was to assess the safety of dutasteride in Korean patients with benign prostate hyperplasia in real life and to elucidate the risk factors related adverse events. METHODS: From December 2004 to January 2010, 3,977 patients were enrolled by 184 urologists. According to post-marketing surveillance regulation, patients were enrolled consecutively. Patients administered dutasteride at least once were included in safety assessment. The incidences of any adverse events and serious adverse events were evaluated. Multiple logistic regression method was used to identify risk factors related to adverse events. RESULTS: The safety assessment included 3,870 patients with the mean age of 67.3 years. The incidence of adverse events was 3.8 %. The most frequent adverse event was impotence (75 cases, 1.9 %), libido decrease (49 cases, 1.3 %), ejaculation disorder (30 cases, 0.8 %), and gynecomastia (5 cases, 0.1 %). The incidence of unexpected adverse events was 0.5 % and cerebral infarction, lung cancer, pulmonary embolism, and diarrhea were reported as serious adverse events. CONCLUSION: In this survey, impotence was the most frequently reported adverse events. Dutasteride was well tolerated in Korean patients with benign prostate hyperplasia. These results updated the safety information and would provide important additional information for prescribers.
Azasteroids ; Cerebral Infarction ; Cholestenone 5 alpha-Reductase ; Diarrhea ; Drug Toxicity ; Dutasteride ; Ejaculation ; Erectile Dysfunction ; Gynecomastia ; Humans ; Hyperplasia ; Incidence ; Korea ; Libido ; Logistic Models ; Lung Neoplasms ; Male ; Prostate ; Pulmonary Embolism ; Risk Factors

BACKGROUND: This study is intended to propose not only to introduce and evaluate the 2 years Clinical Research Coordinator (CRC) professional on-the-job training program that has been implemented in Samsung Medical Center on September of 2009, but also to develop the CRC future education program. METHODS: It is surveyed with self-report type for the 53 trainees, 18 non-trainees, and 17 investigators, the participants worked in Samsung Medical Center, and the major contents of the survey were general characteristics, training program evaluations, CRC qualification evaluation, and job satisfaction. The collected data was analyzed at the 0.05 level of significance by using SAS 9.1 version. RESULTS: The training program is conducted as 4 phases, each phase assessed separately. The Professional A course got the highest satisfaction, and it was deal with quality control (Mean=4.11 ~ 4.33). Most of the investigators answered that the trainees have high priority to be hired in the future (very much=82.45). The non-trainees answered that the training program would be helpful to improve the job competency and qualification (very much=22.2 %, somewhat=55.6 %) and 88.9 % of them answered that they have intention to participate in the training program. Finally, compared to non-trainees, the trainees have more job attachment (P=0.0036) and intention to continue CRC (P=0.0045). CONCLUSION: The CRC professional training program in Samsung Medical Center, as on the job training for 2 years, satisfies the investigators and trainees with positive effect on CRC job satisfaction and job stability. Based on this study, the education program with good quality should be developed considering the characteristics for each institution and close research field.
Humans ; Inservice Training ; Intention ; Job Satisfaction ; Korea ; Phenothiazines ; Quality Control ; Research Personnel

BACKGROUND: This study was aimed to investigate the perception on working conditions and utilization of clinical research coordinators (CRCs) among investigators and sponsors. METHODS: The participants of this cross-section study were 114 investigators and 138 sponsors including clinical research associates (CRAs) who have worked with CRCs. Data was collected with paper or electronic form of self-administered questionnaires and analyzed with descriptive statistics and chi2 test or t test. RESULTS: Among investigators and sponsors, 56.1 % and 95.0 % perceived regular full-time positions as proper type of CRC employment, respectively. Those who perceived monthly salary with incentive as proper payment system were 67.5 % of investigators and 68.8 % of sponsors. The proper salary for 2-year CRCs and 5-year CRCs were significantly higher in sponsors than investigators. Investigators perceived CRCs could handle 3 studies as the same time and 5 studies per year. In regard to the difficulty in utilizing CRCs, 68.4 % of investigators perceived lack of experienced CRCs and 84.8 % of sponsors did frequent turnover. Those who responded pooling CRCs by hospital or clinical trial centers as a good solution to hire CRCs easily were 81.6 % of investigators and 58.0 % of sponsors. CONCLUSION: Almost all investigators and sponsors perceived CRCs were helpful for improving the quality of clinical trials. We recommend each institution or clinical trial centers could introduce the central CRCs' employment and management with proper salary and workload based on the results to maintain experienced CRCs and lessen the turnover of CRCs.
Calcium Hydroxide ; Electronics ; Electrons ; Employment ; Humans ; Motivation ; Surveys and Questionnaires ; Research Personnel ; Salaries and Fringe Benefits ; Zinc Oxide

BACKGROUND: Demands for complicated and long-term administration clinical trials have been increased since investigators actively involved in early stage clinical trials including first-in-human (FIH) trials. Research wards in our clinical trial center were mainly used for phase 1 trials. In order to perform several clinical trials simultaneously during a short period with a minimum number of rooms, beds, and equipment, staffs have to spend a lot of time for efficient operation of limited numbers of facilities. In this study, automated bed-allocation system was developed for efficient scheduling of the research ward based on clinical trial condition and status like experts. METHODS: The system was developed based on clinical trial design, schedule, and the information on research bed and availability stored and updated in database (DB). Automatic assignment system was designed to find an optimal schedule according to the given information using expert rules and algorithms. The optimal solution can be visualized on Gantt chart using C# and Chart FX API. RESULTS: The system was developed to demonstrate the schedule on color chart. It turned out to be well-designed to find an optimal schedule for bed allocation. The system also allows automatic updating of the schedule and information in the DB. CONCLUSION: Automated bed-allocation system developed in this study could save time and improve the efficiency for using space and equipment in clinical trial center. The system can be also applied to similar works or tasks in other fields.
Appointments and Schedules ; Expert Systems ; Humans ; Research Personnel

BACKGROUND: Amlodipine is a third-generation dihydropyridine calcium channel blocker for treating hypertension. Though marketed primarily as a besylate salt, there have been some efforts to find other comparable salts. Among them, maleate is the salt that has been considered favorable for many drugs. The aim of this study was to compare the pharmacokinetics, as well as safety and tolerability of amlodipine maleate with amlodipine besylate. METHODS: This study was open, randomized, two-period crossover design investigated in twelve healthy male volunteers over a 144 h period after administrating two forms of amlodipine 5 mg, respectively. Each period was separated with 2 weeks. Plasma concentrations of amlodipine were determined by liquid chromatography-tandem mass spectrometry. Safety profiles were assessed by vital signs, physical examinations, electrocardiograms, laboratory testing and adverse events monitoring. RESULTS: All subjects were completed this study. Geometric mean ratios (GMRs) of amlodipine maleate/amlodipine besylate of Cmax and AUClast for amlodipine were 0.92 (90 % confidence interval, 0.81 ~ 1.05) and 1.05 (0.96 ~ 1.16), respectively. No serious adverse events were reported, and no clinically relevant changes were observed in safety profiles during this trial. CONCLUSION: Pharmacokinetics, tolerability and the safety were comparable between amlodipine maleate and amlodipine besylate in healthy individuals.
Amlodipine ; Calcium Channels ; Cross-Over Studies ; Dihydropyridines ; Electrocardiography ; gamma-Aminobutyric Acid ; Humans ; Hypertension ; Male ; Maleates ; Mass Spectrometry ; Physical Examination ; Plasma ; Salts ; Vital Signs

BACKGROUND: To grasp the status and future directions, an analysis was done on the articles published in the Journal of Korean Society for Clinical Pharmacology and Therapeutics during recent 19 years. METHODS: All the articles published from 1993 through 2011 were retrospectively analyzed. The number of articles and their language distribution were assessed. The articles were classified according to research types. Authors' affiliations and research fields of articles were also analyzed. RESULTS: The Journal of Korean Society for Clinical Pharmacology and Therapeutics as a semi-annual journal published 353 articles (3,659 pages in total) since its first issue in May 1993. A total of 37 issues were published with the average of 10.1 articles per issue. Most articles were written in the Korean language (94.9 %). In publication type of articles, 13.2 % were review articles, 66.7 % original articles, 18.0 % symposium articles, and the rest other types. In affiliation analysis, most authors were from the academia (91.0 %), next from the industry (5.8 %), and thirdly from the authority (2.3 %). The research field dealt with the highest (28.0 %) was Pharmockinetics/Pharmacodynamics/Pharmacometrics (PPP), core of clinical pharmacology. Many articles in PPP field contained the randomized controlled prospective clinical trials, which are the highest level of evidence, indicating high quality of articles. CONCLUSION: These results suggest that the Journal of Korean Society for Clinical Pharmacology and Therapeutics reflects typically the specialized journal for clinical pharmacology. The internationalization efforts for our journal is also required.
Hand Strength ; Pharmacology, Clinical ; Prospective Studies ; Publications ; Retrospective Studies

The equivalence margin is the largest difference that is clinically acceptable between the test (or experimental) drug and the active control (or reference) drug. This paper discusses the scientific principles, along with the regulatory issues, that need to be addressed when determining the equivalence margin for the biosimilar product. The concept of assay sensitivity is introduced, and the ways to ensure assay sensitivity in the equivalence trial are emphasized. A hypothetical example is presented to show how an equivalence margin is determined. The regulatory agency should carefully assess if the equivalence margin of the biosimilar product was determined using a scientifically valid and clinically relevant approach, not subject to selection bias. This is important because the consumer risk of erroneously declaring equivalence when in fact it is not must be controlled conservatively low in the approval of any biosimilar products.
Dietary Sucrose ; Selection Bias

Over the last two decades, Korean Society of Clinical Pharmacology has performed a pivotal role to have the concept of clinical pharmacology take root in Korea through various academic activities. Clinical pharmacology is not only a research discipline, but also a clinical specialty which aims to provide support for physicians and patients about rational use of drugs. Although it is difficult for any one individual to cover wide range of clinical pharmacology activities, the integrative aspects of the discipline are very important to the development and use of drugs. Recently the world has been faced with serious economic crises and pharmaceutical companies have been shrunken in their research and development, so that clinical pharmacology also has been internationally affected. However, clinical pharmacology has been rapidly grown up in Korea despite the negatively given condition. At this time it is important for physicians in this field to understand the background of our clinical pharmacology in order to complement and develop our current situation for the future. In this review the academic achievement in clinical pharmacology in Korea is valued through looking back our activities for the past twenty years.
Achievement ; Complement System Proteins ; Humans ; Korea ; Pharmacology, Clinical

BACKGROUND: Bivalirudin is a direct thrombin inhibitor for patients with unstable angina undergoing percutaneous coronary intervention. METHODS: A sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS) method was developed and validated for the determination of bivalirudin, in human plasma using nafarelin as internal standard (IS). Chromatographic separation was performed using a Shiseido MG3 mm column (2.0 x 50 mm) with a gradient mobile phase consisting of water and acetonitrile containing 0.1 % formic acid at a flow rate of 0.4 mL/min, and total run time was within 5 min. Detection and quantification was performed by the mass spectrometer using a multiple reaction-monitoring mode at m/z 1091.0 --> 650.3 for bivalirudin, and m/z 662.1 --> 249.3 for IS. RESULTS: The assay was linear over a concentration range of 10 - 10000 ng/mL with a lower limit of quantification of 10 ng/mL in human plasma. CONCLUSION: This method was successfully applied for pharmacokinetics study after intravenous administration of bivalirudin to healthy Korean male volunteers.
Administration, Intravenous ; Angina, Unstable ; Chromatography, Liquid ; Humans* ; Male ; Mass Spectrometry ; Methods ; Nafarelin ; Percutaneous Coronary Intervention ; Pharmacokinetics ; Plasma* ; Thrombin ; Water

BACKGROUND: Erlotinib is a tyrosine kinase inhibitor prescribed for the treatment of non-small cell lung cancer and pancreatic cancer. The aim of this study was to compare the safety and pharmacokinetics (PK) of a generic (test) formulation of erlotinib with those of a reference formulation in healthy volunteers. METHODS: A randomized, open-label, single-dose two-treatment, two-period, two-sequence, crossover study was conducted in Clinical Trials Center, Chungnam National University Hospital with 40 healthy men. Subjects orally received either one 150 mg tablet of the test or the corresponding dose of the reference, and crossover phases were separated by 14-day washout. Plasma samples were collected up to 72 hr post-dose. Plasma erlotinib concentrations were determined by liquid chromatography-tandem mass spectrometry. PK parameters were calculated by non-compartmental analysis. The safety was monitored throughout the study. RESULTS: A total of 21 cases of adverse events were reported. They are mild and relieved without an intervention. There was no serious adverse event. Median times to peak concentration of two formulations were 3.0. Means [SD] for peak concentration (Cmax) and area under the plasma concentration-time curve (AUC) of the test were 1,298 [346] microg/L and 25,318 [7,668] hrxmicrog/L. Those of the reference were 1,193 [378] microg/L and 24,853 [8,419] hrxmicrog/L. Geometric mean ratios (90% confidence intervals) for the test to the reference were 1.10 (1.02-1.18) for Cmax and 1.02 (0.97-1.09) for AUC. CONCLUSION: Two formulations were safe and well-tolerated. PK findings suggest that the test formulation is equivalent to the reference in terms of pharmacokinetics.
Area Under Curve ; Carcinoma, Non-Small-Cell Lung ; Chungcheongnam-do ; Cross-Over Studies ; Erlotinib Hydrochloride ; Healthy Volunteers* ; Humans ; Male ; Mass Spectrometry ; Pancreatic Neoplasms ; Pharmacokinetics ; Plasma ; Protein-Tyrosine Kinases ; Therapeutic Equivalency*