Interindividual variability in the efficacy and toxicity of chemotherapy is associated with polymorphisms in genes encoding drug-metabolizing enzymes, transporters, or drug targets. Pharmacogenomics is the study of the hereditary basis of these interindividual differences and aims to identify genetic factors to predict toxicity and therapeutic outcomes. There exist several clinically relevant examples of the utility of pharmacogenomics that associate specific genetic polymorphisms in drug metabolizing enzymes and drug target enzymes. This review discusses the current and future applications of pharmacogenomics in clinical cancer therapy.

Clinical trials are the most expensive and time consuming stages in the process of drug development. It is widely accepted that e-clinical technologies will have the most immediate and noticeable impact on drug development by streamlining clinical trials. Although vast majority of clinical trials are still being conducted with paper-based process, information technology is contributing to improve the clinical trial research process. Internet allows real time data collection and enhanced interactivity between study participants and site personnel. Small handhold devices, such as Personal Digital Assistants (PDAs) and cell phones, are often used to collect subject information easily and directly from subjects. Wireless internet links handhold devices to a central computer at any time and any place. Our experiences of PDA developing clinical trial data collection system and XML based e-Clinical Report Form reveals the effectiveness of technology for clinical trials. Our PDA based clinical trial data collection system can enter the data on the PDA and simultaneously transfer to the database through wireless internet. This system aims to examine the feasibility of PDAs as an innovative method for efficient and effective clinical trial data collection. Sixty four irritable bowel syndrome patients are randomly selected and divided into two groups; the control group (paper based user) and the intervention group (PDA based user). Response rate, response completeness and input error are measured to evaluate the effectiveness of the PDA clinical trial management system. Response rate of the control group (595, 94.4%) is higher than the intervention group (487, 77.3%). In addition, electronic Case Report Form (e-CRF) system was developed using Acrobat Live Cycle Forms. This system intends to provide user friendly electronic data collection system Just like paper case report form. Our efforts show that the information technology is able to improve data quality, decrease data input error, and ultimately improve the effectiveness of clinical trial data management.

Fharmacokinetic/pharmacodynamic (PK/PD) modeling links dose-concentration relationships (PK) and concentration-effect relationships (PD), thereby facilitating the description and prediction of the time course of drug effects resulting from a certain dosing regimen. This review gives some background information on PK/PD modeling and what non-linear mixed effects models are, why they can be useful in analysing repeated measures and what makes analysing such data challenging. NONMEM perform this kind of analysis, and will be reviewed briefly in this paper. In all phases of preclinical and clinical drug development, application of PK/PD modeling concepts are potentially beneficial. And broader application of PK/PD concepts in clinical therapy will provide a more rational basis for personalized medicine.

Background: Amlodipine is a dihydropyridine calcium antagonist used for the treatment of hypertension and angina. Amlodipine adipate is a newly developed salt formulation of amlodipine. The purpose of this study was to compare the pharmacokinetic and pharmacodynamic characteristics of amlodipine adipate with those of conventional amlodipine besylate in healthy subjects. Methods: The study was conducted as a single blinded, block dose randomized, two-way crossover design. Twenty-four subjects were enrolled, twelve subjects each for the 5 mg dose group and the 10 mg dose group. Subjects were administered single oral dose of amlodipine adipate and amlodipine besylate, in a randomized sequence, with two weeks washout period between the two treatments. Serial blood samples were collected till 120 hours after drug administration. Plasma concentrations of amlodipine were analyzed by liquid chromatography tandem mass spectrometry. Individual pharmacokinetic parameters were calculated by noncompartmental methods and the pharmacokinetic parameters were analyzed by analysis of variance. Ambulatory blood pressure and computerized impedance cardiography were measured till 24 hours after drug administration. The pharmacodynamic parameters were analyzed by repeated-measures analysis of variance. Results: In the 5 mg dose group, the ratios of $AUC_{last}$ and $C_{max}$ of amlodipine adipate to amlodipine besylate were 0.93 and 0.89, respectively. In the 10 mg dose group, the ratios of $AUC_{last}$ and $C_{max}$ of amlodipine adipate to amlodipine besylate were 1.01 and 1.09, respectively. Regarding pharmacodynamic results, there were no significant differences in systolic blood pressure, diastolic blood pressure, pulse rate, or in change of total peripheral resistance between amlodipine adipate and amlodipine besylate at doses of both 5 mg and 10 mg. Conclusions: We concluded that amlodipine adipate and amlodipine besylate showed similar pharmacokinetic and pharmacodynamic characteristics.

Background: Ibandronate is a nitrogen-containing bisphosphonate and used for the treatment of hypercalcemia of malignancy and postmenopausal osteoporosis as a potent Inhibitor of osteoclast-mediated bone resorption. This study was performed to evaluate pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of ibandronate after a single intravenous (iv) infusion in healthy subjects. Methods: The study was conducted as a double blinded, randomized, placebo controlled, parallel group study in twenty-six healthy Korean subjects (13 males and 13 females). Subjects were randomized into one of three treatment groups of 2 mg, 6 mg, or placebo, with 10, 10, and 6 subjects in each group, respectively. Blood and urine samples for PK assessments were collected till 24 hours after the start of a 60 minute iv infusion. For PD assessments, CTX (Type I Collagen-linked C-telopeptide) and NTX (Type I Collagen-linked N-telopeptide) were measured in both serum and urine until 4 days after the infusion. Results: The area under the concentration-time curves from time zero to infinity ($AUC_{0-\infty}$) were $333.4\;{\pm}\;46\;(Mean\;{\pm}\;SD)\;ng{\cdot}h/mL$ for the 2 mg group, and $939.1\;{\pm}\;267.1\;ng{\cdot}h/mL$ for the 6 mg group. The values of mean clearance were 6.1 L/h and 6.9 L/h in the 2 mg and 6 mg group, respectively. Four days after the infusion, urinary CTX was decreased by 71.5% (2 mg) and 93.5% (6 mg group) from baseline (both P < .001). Other PD parameters were also significantly decreased in active treatment groups compared with the placebo group. Conclusions: Pharmacokinetic parameters exhibited linear properties regrding dose. Pharmacodynamic parameters as markers of bone turnover were significanly decreased from baseline in the active treatment groups.

연구배경: 고압산소치료는 호흡기와 순환기계를 포함하여 여러가지 생리학적 변화와 연관되어 있다. 이러한 변화가 caffeine의 약동학에 미치는 영향을 4명의 건강자원자에서 평가하였다. 방법: 커피를 이용하여 경구로 카페인을 투여하였으며 7일간의 휴약기간을 두고 정상기압때와 고압산소치료때 카페인의 약동학을 교차실험하였다. 고압산소치료표는 국내에서 가장 흔히 사용되는 것을 사용하였다. 혈중 카페인농도는 고성능액체크로마토그래피를 이용하여 측정하였으며 얻어진 약동학적 경수는 비모수적 방법으로 평가하였다. 결과: 평균 농도곡선하면적과 최고농도는 정상기압시 $34.27{\pm}0.1\;{\mu}g{\cdot}hr/ml$, $4.43{\pm}0.64\;{\mu}g/ml$였으며 고압산소 치료시 $45.65{\pm}9.89\;{\mu}g{\cdot}hr/ml$, $5.72{\pm}0.61\;{\mu}g/ml$였다. 평균 청소율 및 소실반감기는 정상기압시 $120.09\;{\pm}\;37.56\;ml/hr$, $3.75\;{\pm}\;0.84\;h$였으며 고압산소치료시 $85.36\;{\pm}\;17.83\;ml/hr$, $4.03\;{\pm}\;1.13\;h$로 나타났다. 그러나, 통계적으로 유의한 차이는 없었다 (p > 0.05). 결론: 일반적인 고압산소치료는 카페인의 약동학에 유의한 영향을 미치지 않았으나 명확한 상호작용의 규명을 위하여 추가적인 연구가 필요할 것으로 사료된다.

Background: Nitrates are the most frequently used anti-anginal drug in clinical practice. But, it has many side effects like hypotension, headache and dizziness. Nicorandil, a potassium channel opener, has not only nitrate-like effects also many cardioprotective effects. In this study, we compared the side effects, compliance and clinical effects between nitrate and nicorandil in patients with ischemic heart disease. Methods: Patients who were prescribed with isosorbid dinitrate 120mg once daily or nicorandil 5mg t.i.d at out patient clinic were investigated in this study. All patients were discharged after acute management of acute coronary syndrome. We reviewed medical records and analyzed side effects, compliance and major cardiovascular events (death, non-fatal myocardial infarction, re-admission and coronary revascularization). Results: Total 866 patients (533 nitrate group and 333 nicorandil group) were included in this study. The mean follow up duration was 18 months. During treatment, the drugs were discontinued in 19% of each group. The most common cause of drug cessation was hypotension in nitrate (13.7%) and headache in nicoradil group (12.5%). There were 34 (6.4%) major adverse cardiac events in nitrate group and 21 (6.3%) in nicorandil group, and it was not significantly different. Conclusions: In this retrospective observational study, nitrate and nicorandil showed similar rate of side effects, drug cessation and clinical effects on cardiovascular events. But, we need more time to see the difference of long-term cardiovascular effects of these drugs.

As the number of multicenter clinical studies has been increased very rapidly in recent years, the necessity of joint institutional review board (IRB) gets realized for making review process more efficiently. Large private joint IRBs such as Western IRB have been established and providing wide range of IRB activities in the United States. In Taiwan, Joint IRB was founded as a non-profit institute, which has been performing the review activities for premarketing multicenter clinical trials. In the United Kingdom, multicenter clinical studies should be reviewed by Multi-centre Research Ethics Committee. It is institutionalized that any IRB recognizes and accepts the review result of other Institution's IRB in Australia. The profit IRB, non-profit IRB, ad hoc IRB, regional IRB, or mutual recognition can be considered as models of joint IRB in Korea.

?Background: Rapidly increasing scale of multicenter clinical studies (MCTs) is pressing the need of joint institutional review boards(IRB) in Korea. The purpose of this survey was to evaluate demand for joint IRE and appropriate form. Methods: We constructed a questionnaire on the present IRE state on MCTs, agreement for joint IRB, ideal organization and operation method. This questionnaire was sent by mail to active clinical trial investigator group and head or secretary of all IREs registered to KFDA. Results: Totally 187 participants replies, with 67.4% of investigators and 32.6% of head of IRBs. 79.9% responders reported repeated review on same MCT among each participating IRBs, and proportion of for and against of joint IBE were 74.3%, 24.1% respectively. Discussion: Construction of joint IRB is supposed to have various strengths such as activation of MCTs due to reduced unnecessary review process, efficacy increment due to standardized review standards and resolutions. Before, preparatory works are necessary for successful achievement.