Introduction : Hyperlipidemia is closely related to the generation of coronary heart disease (CHD). The objective of this study was to compare the efficacy of acipimox and fenofibrate for the treatment of hyperlipidemia. Methods : The study performed a retrospective comparison of acipimox (250 mg TID) and fenofibrate (200 mg/day) by comparing the means of changes in total cholesterol, triglyceride, HDL-C, LDL-C levels, and TC/HDL-C ratio at 3, 6, and 9 months of the treatments. Results: A total of 103 patients (41 in acipimox group and 62 in fenofibrate group) were evaluated. Acipimox- and fenofibrate-treated group were comparable with respect to patient demographic characteristics. After treatments both acipimox and fenofibrate produced a significant reduction in total cholesterol(9.7% with acipimox; 11.3% with fenofibrate), triglyceride levels (52.6% with acipimox, p<0.001; 54.3% with fenofibrate, p<0.001) and TC/HDL-C ratio(15.2% with acipimox; 18.0% with fenofibrate) from baseline. HDL-C levels after treatments increased by 8.4% and 9.3% with acipimox and fenofibrate, respectively. Both drugs did not produce a significant reduction in LDL-C levels (4.4% with acipimox; 2.0% with fenofibrate) after treatments. The mean changes of total cholesterol, triglyceride, LDL-C, HDL-C levels and TC/HDL -C ratio were not significantly different between the two drugs. Conclusion : Both acipimox- and fenofibrate- treated groups experienced significant changes in total cholesterol, triglyceride, HDL-C, and TC/HDL -C ratio from the baseline 따ter treatments.

Background : According to the study conducted on hospitalized patients in the United States, there were more than 2,000,000 serious ADRs in hospitalized patients, causing over 100,000 deaths annually. If true, then ADR is the $4^{th}$ leading cause of death in the United States. In Korea, ADR monitoring system has not been activated. ADR monitoring system in the Seoul National University Hospital and Korean Medical Association, representing the nationwide clinicians, was initiated on May 2001 and on May 2002, respectively. Until Oct $1^{st}$ 2002, only 30 cases, 16 cases from the Seoul National University Hospital and 14 cases from the Korean Medical Association were reported. At present, rapid and valid review, resulting in helpful feedback to the reporters is essential for the activation of ADRs monitoring system in Korea. In the same context, the algorithm, easy-to-use and in Korean, for the initial causality assessment became necessary. Methods : In this study, a draft algorithm was constructed after reviewing the three current algorithms: Naranjo, French, and RUCAM. Then a study was conducted to evaluate the validity and reliability of the algorithm. The test was done with three target users, a physician majoring in internal medicine, a general physician and pharmacist majoring in Pharmacoepidemiology, assessed the causality of the reported 26 ADR cases with the algorithm as test reviewers. Finally, the results were compared with the gold standard, the decision of the Committee for Drug Safety within the Korean Medical Association. Results : The average sensitivity and specificity was 96%, 38% respectively. According to the result of the test-retest reliability with Pearson correlation coefficient, two of 3 test reviewers showed significant correlations. Conclusion : The Korean Algorithm seemed to be valid and reliable. But it is important to make an additional effort to modify and update the Korean Algorithm. The development of the Korean Algorithm must be the first step to establish the Adverse Drug Monitoring System in Korean.

Objectives : This study was designed to review the Drug prescription pattern of anti epileptic drugs for elderly inpatients. Methods The study population comprised inpatients of community hospitals who were members of the Korean Elderly Pharmacoepidemiologic Cohort(KEPEC), aged 65 years or over, beneficiaries of the Korea Medical Insurance Corporation(KMIC) and residing in Busan city in 1993. The drug prescription information was collected from the claims data of hospitals where the cohort members received medical care between January 1993 and December 1994. The database included person머 identifier, age, sex, diagnosis, the name of drugs, dosage, the date of prescription and the code number of medical institution where the patients were admitted. The distribution of prescription by each antiepileptic drugs was analysed. Combined prescription of antiepileptic drugs and the possibility of drug interaction with antiepileptic drugs were also analysed. Results : The number of patients prescribed antiepileptic drugs was 208(5.6%) among elderly inpatients within KEPEC members. The most frequently prescribed antiepileptic drug was phenytoin(41.8%), followed by phenobarbital(19.8%) and carbamazepine(18.0%). The proprotion of combined prescription between antiepileptic drugs was 14.2%. Combination with phenytoin and valproic acid was most frequently prescribed. The rate of combined prescription of antiepileptic drugs and drugs that could induce risk from drug interaction with antiepileptic drugs was very high, phenytoin(86.2%), phenobarbital (80.0%), valproic acid(78.3%), respectively. That of carbamazepine(12.0%) was lower than other antiepileptic dugs. Conclusion : There were a lot of many comedications between antiepileptic drugs and several drugs with drug-interaction in this study. This situation was able to serious problem because antiepileptic drugs in elderly inpatients could induce adverse drug reactions and hazardous drug-drug interaction. This study proposes that antiepileptic drugs should be used carefully in the elderly.

Background : The effect of age on the activity of drug metabolizing enzymes has not been studied thoroughly. We examined the effect of age on the metabolic activity of CYP2D6 and N-acetyltransferase. Methods : Metoprolol and isoniazid were used as probe drugs of CYP2D6 and N-acetyltransferase, respectively. We measured metabolic ratios of metoprolol and isoniazid in 80 subjects of $21{\sim}85$ years old. Metabolic ratio(MR) of metoprolol was defined as the ratio of $metoprolol/{\alpha}-hydroxymetoprolol$ in the urine collected for 8 hours after the administration. Isoniazid/acetylisoniazid was used for MR of isoniazid. Concentrations of parent drug and metabolite were assayed by HPLC simultaneously. General linear model in SAS $8.1^{\circledR}$ was used for the statistical analysis 따ter visual exploration. Metabolic ratios were log-transformed to be normalized for analysis. Results : Demographic characteristics were similar between groups of metabolic activities. MRs of both drugs were not significantly different betweeb groups by age, sex and smoking. Mean MR of metoprolol for adult group(age<65) was 0.85$(90%\;CI:\;0.48{\sim}1.48)$ times that of elderly group$(age{\geq}65)$ and mean MR of isoniazid for adult group was 1.01$(90%\;CI:\;0.57{\sim}1.79)$ times that of elderly group. The proportions of poor metabolizer(adult: elderly=1.75%: 0 %) or slow acetylator(adult: elderly=17.54%: 17.39%) were not different between age groups. The effect of age on the metabolism was not significant even when it was adjusted with phenotype(p-value=0.58 and 0.54 for metoprolol and isoniazid, respectively). Conclusion : The effect of age on the metabolic activities of CYP2D6 and N-acetyltransferase was not significant. Therefore, dosage adjustment according to age may not be necessary for the drugs that are eliminated through these enzymes and a confirmatory study is need.

The enormous cost, intensive time, and constant efforts are required the drug discovery and development of bringing new drug products to the marketplace. The past several years, KFDA approved new drugs developed by local pharmaceutical industries; that is Sunppla, Factive etc. In addition to, investigational new drug application (IND) was established to accelerate new drug development and harmonize with international standards in 2002. At this point of time it is urgent problem to develop ability of reviewing new drug applications (NDAs) scientifically and appropriately to ensure that new drugs are safe and effective. There are many scientific issues embedded in new drug approval process from non-clinical studies to phase 3 clinical trials; 1) sample size, 2) application of end point, 3) statistical method, and etc. However the overall relation between protocols/reports of clinical trials and the characteristics of domestic medical system has fully not been studied. There is also, no references or data for the point to be considered in drug approval process. On this background, the objectives of this study are introduction of guidelines for the requirement for approval or evaluation of safety/efficacy in other countries and presentation how to practice clinical trial for new oncologic products in the present situation of clinical trial. We hope that the guidelines contribute to providing methods of clinical trials and procedures, and evaluating method to develop chemotherapeutic agents.

Pregnancy is not associated with increased risk for infectious disease, except for urinary tract infection, chorioamnionitis, endometritis and puerperal sepsis which are results of altered physiology during pregnancy. There are several numbers of infectious diseases in which the rational antimicrobial therapy could not be delayed to the postpartum periods. The first consideration of antimicrobial therapy in pregnant woman is the physiologic change associated with the normal pregnancy; Usually the plasma volume increased with enlarged both hepatic and renal clearance of the drugs. The maternal capacity to metabolize toxic substances decreases as the gestational age increases. Few things are known about the fetal pharmacokinetics of antimicrobial agents, but that the overall contribution seems not to be considerable and the maternal serum level monitoring is enough to keep the fetus from adverse effects. The United States Food and Drug Administration (FDA) had recommended a criteria to select antimicrobial agents during pregnancy according to the known data on the fetal risks of each drugs giving a classification from A to D and X. Antimicrobial agents like penicillins, cephalosporins and erythromycin bases that belong to the class B can be safely used to treat maternal infections. Class C with no adequate human data, should not be primarily considered. But any exposure to the class C antimicrobial agents does not necessarily signify increased fetal risk so that therapeutic abortion should be considered. Even class D drug may be necessary to treat some specific infections, if the benefit is proven. The oldest antimicrobial agent penicillins with well known pharmacokinetics is safely prescribed for the treatment of syphilis and susceptible streptococcal infections. The combination regimen of ampicillin-sulbactam is safe despite known evidence of Cocms' positivity without fetal anomaly. Cephalosporins add good pharmacokinetics properties to the equivalent safety to penicillins. Methyltetrazolethiol group toxicities should be considered but related fetal toxicity is not associated. In case of metronidalzole, though potential for carcinogenesis in rodents is known, no human cancer is known till present, and many controlled study on exposed pregnant woman did not repαt increased fetal risk. Treatment of tuberculosis during pregnancy is strongly recommended to reduce the rate of neonatal transmission, congenital tuberculosis and abortion, pre-eclamps, dystorcia.

Since the ICH E5 guidelines were adapt어 in ICH countries in 1998, the bridging data package became one of new drug approval requirements in Korea far the drugs developed in other countries. However the guideline does nat identify methods far bridging between two different populations. Korea is being involved in mare multinational clinical trials with New Chemical Entities that were developed in US and Europe. However there have been few attempts ta use the studies for bridging purposes and the Korean clinical data from the studies were seldom utilized in bridging far NDA due to the limited number of Korean patients that doesn't have sufficient statistical power far subgroup analyses. There are several literature that proposed statistical approaches and methodology to bridge global clinical data to a new population. This paper suggests possible options how to plan or utilize a multinational study to use the Korean subgroup data far bridging far New Drug Application in Korea.