Non-commercial investigator-initiated clinical trials are different from commercial trials sponsored by company according to trial purpose. Irrespective of Korean government’s efforts there are no definite guidelines for investigator-initiated clinical trials using unapproved drugs such as gene materials except clinical research using cell products and market-approved drugs. In USA and EU, the clinical trial results from non-commercial process could be used for marketing approval, if it is proven that the clinical trial has been done according to ICH-GCP guideline. However, In Japan, "chiken (clinical trial)" and "clinical research" are separated. In the clinical research except stem cell and gene therapy, the scientific and ethical aspects of new technology or therapeutics are reviewed only by the institutional review board (IRB), not by the regulatory agency. In the case of "chiken", the applicant has to submit a clinical trial application to the Pharmaceuticals and Medical Devices Agency (PMDA). To reduce administrative burdens and encourage the investigator-initiated trials, investigator-initiated chiken process was developed in Japan. Therefore, to improve and promote the clinical trials initiated by investigator in Korea, it is time to focus on Japan's investigator-initiated chiken process.

Background: Recently, researches on the pharmacological activity of natural substance are increasing. Acorn is one of promising candidates which is expected to exert anti-aging effects through anti-oxidant activity of gallic acid (GA). Methods: Crude extract was obtained from acorn which was harvested in Korea, 2009. After random allocation of 18 subjects into different dose groups (1g, 2g and 4g daily), the extract was given orally for 21 days. Full pharmacokinetic studies (0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hr after dose) were done after the first and last doses. The LC/MS/MS system was used to determine the GA in the extract and plasma samples. The results were analyzed using mixed effect methods NONMEM (Ver.6.2). Results: GA content in the extract was 0.27% (m/m). An one-compartment model was used to describe the PK property. Oral Clearance (CL/F) was 153 L/hr with the between-subject variability (BSV, as RSV %) of 44.5%. The estimated volume of distribution (V/F) was 231 L with the BSV of 37.0%. The population estimates of absorption rate constant (Ka) was $3.23\;hr^{-1}$ and the relative bioavailability of 4g dose group was 75.4% compared to the other groups. Conclusion: Population pharmacokinetic parameters for gallic acid were successfully estimated. According to the parameters, it was expected that gallic acid would not be accumulated after repeated once-daily dosing and the extent of gallic acid absorption would be limited in the 4g dose group.

Background: Interferons (IFNs) are proteins made and released by lymphocytes in response to the presence of pathogens and used in the treatment of hepatitis B or C virus. The purpose of this study is to investigate the safety, pharmacokinetics and pharmacodynamics of a pegylated interferon alpha-2a formulation. Methods: This study was a randomized, open-label, 2-period, crossover design. Each group had 17 subjects who took $180\;{\mu}g$ of $PEGASYS^{(R)}$ as a reference formulation and DA-3021 as a test formulation with a washout period of 21 days. Blood samples were obtained over 336 hours after the dose in each treatment period. Blood concentrations of interferon were analyzed using the enzyme-linked immunosorbent assay (ELISA). The primary pharmacokinetic parameters were $C_{max}$ and $AUC_{last}$. The pharmacodynamics were assessed by 2',5'-OAS (oligoadenylate synthetase) using a radioimmunoassay (RIA). The primary pharmacodynamic parameters were $E_{max}$ and $AUE_{last}$. Results: Thirty four healthy male volunteers participated in the study and completed both treatment periods. The 90% confidence intervals for the geometric mean ratios of the pharmacodynamic parameters (test : reference drug) were 0.95-1.09 for $AUE_{last}$ and 0.92-1.05 for $E_{max}$, lying within the bioequivalence range of 0.8-1.25, while the pharmacokinetics parameters were not included within the equivalence range. Most common adverse events were flu-like symptoms, with no serious adverse event reported. Conclusion: The results assessed by the bioequivalence criterion indicated that the pharmacodynamics of DA-3021 was equivalent to that of $PEGASYS^{(R)}$.

Background: Naftopidil is a selective ${\alpha}_1$ adrenergic receptor antagonist which is used for the treatment of dysuria caused by benign prostatic hyperplasia. We investigated the pharmacokinetic characteristics and tolerability of naftopidil after a single oral dose in healthy Korean male volunteers. Methods: Sixteen subjects were allocated into two groups (8 for naftopidil 50 mg and 75 mg, 8 for naftopidil 25 mg and 100 mg). Serial blood samples for pharmacokinetics were collected up to 24 hours after drug administration. Naftopidil plasma concentrations were determined by HPLC. The pharmacokinetic parameters were calculated by noncompartmental methods. Tolerability assessments including vital signs, 12-lead ECG, clinical laboratory parameters, and adverse events were conducted. Results: The median time of maximum observed plasma concentration ($T_{max}$) was 0.5 h in all dose groups. The maximum plasma concentration ($C_{max}$) of 25, 50, 75 and 100 mg dose group were $44.0\;{\mu}g/L$, $88.9\;{\mu}g/L$, $114.3\;{\mu}g/L$, and $179.5\;{\mu}g/L$, respectively. The area under the concentration-time curve to the last measured concentration over the limit of quantitation ($AUC_{last}$) of respective dose groups were $71.1\;{\mu}g{\ast}h/L$, $178.7\;{\mu}g{\ast}h/L$, $298.3\;{\mu}g{\ast}h/L$, and $342.6\;{\mu}g{\ast}h/L$, respectively. Conclusion: The results of this study indicate that the systemic exposure of naftopidil expressed $AUC_{last}$ and $C_{max}$ was increased dose proportionally, and all doses. Up to 100 mg were well tolerated without serious adverse events in healthy Korean male volunteers.