Despite the importance of clinical trials in developing a new drug, paper based clinical trial is still costly and time-consuming. The process of a clinical trial has not kept up with available information technologies. We identify two major problems in paper based clinical trial. They are time delay and poor error control. To solve the problems information technologies are used in certain areas of clinical trial, but it is still restricted and partially helpful. This paper first explains the two problems in the process of paper based clinical trial and introduces four available information technologies that can help clinical trial in implementing electronic clinical trial (ECT), where information technologies are used in the whole process of clinical trial.

The ATP-binding cassette (ABC) transporters are involved in a variety of biologic processes in human and other organisms. Currently, 49 ABC transporter genes were identified in human genome and classified into 7 subfamilies according to their sequence homologies. The ABC proteins provide nutrients to the cells, protect them from a wide range of toxic compounds, and regulate basic biologic processes of essential organs such as alimentary tract, liver, lung and immune systems. Consequently, mutations affecting ABC-transporters have been found to be the underlying causes for a large number of human inherited diseases and individual diversity of drug responses. For example, aberrant membrane transport caused by mutations in CFTR gene is associated with a wide spectrum of respiratory and digestive diseases as well as cystic fibrosis. A group of ABC genes code the multi-drug resistance (MDR) and multidrug resistance-related proteins (MRPs) , which function as xenobiotic transporters. MDRI was originally identified as a gene that confers multi-drug resistance to cancer cells. The MRPs were discovered as a second type of drug pump in cancer cells exhibiting multi-drug resistance not caused by MDRl. However, recently it was found that they are the native exporters having physiological role of protecting organism from various toxic substances including commonly prescribed medications. Thus, identifying the individual genetic variations of these transporters carries significant meaning in pharmacotherapy of post-genomic era, since such genetic variants are likely to be an important source for the inter-individual variability in pharmacokinetics and pharmacodynamics of many drugs. Future investigations in large scale analysis of ABC transporter genes will provide the basis for understanding the pathogenesis of many genetic disorders and for elucidating the molecular mechanisms related to individual diversity of drug responses.

According to the ICH GCP, an audit is defined as 'a systematic and independent examination of trial-related activities and documents to determine whether the evaluated trial-related activities were conducted and the data were recorded, analyzed, and accurately reported according to the protocol, sponsor's SOPs, GCP, and the applicable regulatory requirement(s).' An audit usually starts with planning: then, follow in-house evaluation, actual survey at the center, preparation of the audit report, and submitting it, in that order. The audit conducted by the Clinical Research Center at Seoul National University Hospital identified some errors most frequently observed: absence of source documents (63.9% of total subject center), discrepancies between CRFs (Case Report Form) and source documents (61.1%), inappropriate handling of essential documents (52.8%), informed consents inappropriately acquired (36.1%), and violations of the protocol (22.2%). Like this well-planned and standardized audit would give a way to more qualified clinical trials.

Background: Irbersartan, an orally active antihypertensive agent, effectively reduces blood pressure by blocking angiotensin II receptors without any significant adverse effects. The purpose of this study is to compare the antihypertensive efficacy, safety and tolerability of irbesartan and enalapril in hypertensive patients. Methods: In this two centers, double-blind, randomized, non-inferiority study, the efficacy, safety and tolerability of once-daily irbesartan(150mg) versus once-daily enalapril(10mg) were evaluated over 8 weeks in 67 patients who had diastolic pressure between 95mmHg and 114mmHg on two measurements. If trough sitting diastolic blood pressure was equal to or greater than 90mmHg after a 4-week treatment period, the dosage for both study drugs was doubled until the end of the study. Baseline pressures, antihypertensive effect, side effects, laboratory findings were compared before and after treatment. Results: Data from 57 of 67 patients were eligible for intention to treat analysis. After the 8 weeks treatment with dose titration, mean reductions in peak sitting diastolic blood pressure were 11.9mmHg(95% confidence interval 7.61 -16.13) with irbesartan and 10.9mmHg$(95%\;confidence\;interval\;7.05{\sim}14.70)$ with enalapril. There was no significant difference between the two treatments in the percentage of patients achieving an effective blood pressure reduction or in the degree of change in mean systolic and/or diastolic blood pressure. Safety profiles were also similar between treatments. Conclusions: The antihypertensive efficacy of once-daily administration of irbesartan is non-inferior to that of enalapril in hypertensive patients. Both irbesartan and enalapril are well tolerated with similar safety profiles.

Background: This study was conducted to evaluate the bioavailability of Fluconazole formulation in healthy Korean volunteers. Furthermore, the bioequivalence of $Flukan^{\circledR}$ capsule, a fluconazole preparation from Korea United Pharm, Inc., was determined. Methods: The study employed a randomized, two-way crossover Latin square design with a two-week washout period. The test product was $Flukan^{\circledR}$ capsule (Korea United Pharm Inc., South Korea) and the reference was $Diflucan^{\circledR}$ capsule (Pfizer Inc.). The two products were administered in 150 mg single oral doses into 26 healthy Korean volunteers. Serial blood samples were collected for a period of 120 hours. Plasma fluconazole concentrations of the two brands were measured by HPLC using UV detector, and the pharmacokinetic parameters including $AUC_t,\;C_{max},\;T_{max}$, and half-life were determined from plasma concentrations of both formulations. Results: Both formulations were well tolerated in 26 volunteers. Mean $AUC_t,\;C_{max}$ of $Flukan^{\circledR}$ capsule were 1.068 $(90%\;confidence\;interval:\;1.0057{\leq\delta\leq}1.1349)$ and 1.017 $(90%\;confidence\;interval:\;0.9633{\leq\delta\leq}1.0749)$ compared to those of $Diflucan^{\circledR}$ capsule. Mean half-life of $Flukan^{\circledR}$ capsule was $30.41{\pm}5.44$ and that of $Diflucan^{\circledR}$ capsule was $30.74{\pm}5.86$ hr. The powers $(1-{\beta})$ for $AUC_t\;and\;C_{max}$ were above 90%. The pharmacokinetic parameters $(AUC_t,\;C_{max},\;T_{ max})$ were analyzed statistically with K-BE test 2002 (KFDA). Conclusion : No significant differences between two formulations were observed in terms of $AUC_t\;and\;C_{max}$, the main pharmacokinetic parameters used for bioequivalence evaluation. The results satisfied the bioequivalence criteria of KFDA guidelines, and $Flukan^{\circledR}$ capsule was determined to be bioequivalent to $Diflucan^{\circledR}$ capsule.

Objective : To compare the efficacy and safety of S-adenosyl-methionine (SAMe) and ibuprofen in the treatment of patients with knee osteoarthritis. Methods : Sixty patients with knee osteoarthritis (OA) were enrolled in this study. Patients received a daily oral dose of 1200mg of SAMe and 1200mg of ibuprofen for 4 weeks Treatment efficacy was evaluated with clinical parameters as Lequesne's functional index and visual analog scale (VAS) of pain. Adverse effects were monitored from patient interviews and blood sampling. Results: The treatment efficacy evaluated by clinical parameters was not different in both groups. Gastrointestinal adverse effects were more frequently observed in ibuprofen group than in SAMe. Conclusion : SAMe was equally effective to ibuprofen in efficacy and better tolerated in short term treatment of patients with knee OA.

Background: Tegaserod is a selective partial agonist at the $5HT_4$ receptor. Tegaserod belongs to a new class of agents in development for the treatment of functional motility disorders of the gastrointestinal(GD tract. This Phase I clinical study was conducted to evaluate the safety and pharmacokinetics(PK) of tegaserod in Korean for bridging foreign clinical data. Methods: A randomized, double blind, placebo controlled, multiple oral dosing(2 mg, 6 mg, twice a day for 7 days) study was conducted in 32 healthy Korean volunteers(M:F=16:16). Serial blood samples for pharmacokinetic analysis were taken. Safety evaluation was performed by adverse event monitoring, physical examination including vital signs, ECG and clinical labororatory analysis. Results: Plasma concentration of tegaserod reached peak levels $1.0{\sim}1.5$ hours after single and multiple dose administration and declined with a terminal half life of about 12 hours. PK parameters of 2 mg group were not calculated well due to low plasma concentration. Tegaserod showed linear pharmacokinetic characteristics, and little accumulation occurred after multiple administrations. There were no gender differences in PK parameters. Neither serious nor dose-limiting adverse events were observed. PK of tegaserod in Koreans was comparable to Caucasian data. Conclusion: Tegaserod was found to be safe and showed similar PK characteristics to Caucasians. This study demonstrates comparability between Korean and Caucasian healthy subjects in the PK of tegaserod and supports the use of Caucasian data in the evaluation of PK, safety, and efficacy for Korean patients.