• 대한임상약리학회:학술대회논문집
• /
• 1999.12a
• /
• pp.44-44
• /
• 1999

• Genomics & Informatics
• /
• v.16 no.3
• /
• pp.52-58
• /
• 2018

In this report, we present a case study of how pharmacogenomics and pharmacometabolomics can be useful to characterize safety and pharmacokinetic profiles in early phase new drug development clinical trials. During conducting a first-in-human trial for a new molecular entity, we were able to determine the mechanism of dichotomized variability in plasma drug concentrations, which appeared closely related to adverse drug reactions (ADRs) through integrated omics analysis. The pharmacogenomics screening was performed from whole blood samples using the Affymetrix DMET (Drug-Metabolizing Enzymes and Transporters) Plus microarray, and confirmation of genetic variants was performed using real-time polymerase chain reaction. Metabolomics profiling was performed from plasma samples using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. A GSTM1 null polymorphism was identified in pharmacogenomics test and the drug concentrations was higher in GSTM1 null subjects than GSTM1 functional subjects. The apparent drug clearance was 13-fold lower in GSTM1 null subjects than GSTM1 functional subjects (p < 0.001). By metabolomics analysis, we identified that the study drug was metabolized by cysteinylglycine conjugation in GSTM functional subjects but those not in GSTM1 null subjects. The incidence rate and the severity of ADRs were higher in the GSTM1 null subjects than the GSTM1 functional subjects. Through the integrated omics analysis, we could understand the mechanism of inter-individual variability in drug exposure and in adverse response. In conclusion, integrated multi-omics analysis can be useful for elucidating the various characteristics of new drug candidates in early phase clinical trials.

• Journal of Pharmaceutical Investigation
• /
• v.35 no.3
• /
• pp.179-185
• /
• 2005

Acebrophylline is a compound produced by salifying ambroxol with theophylline-7 -acetic acid. After acebrophylline administration, the salt splits into these two components which feature a peculiar pharmacokinetic behavior, an adequate ambroxol and a low theophylline-7-acetic acid serum levels. The purpose of the present study was to evaluate the bioequivalence of two acebrophylline capsules, Surfolase (Hyundai Pharm. lnd. Co., Ltd.) and Burophil (Kuhnil Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of ambroxol from the two acebrophylline formulations in vitro was tested using KP VIII Apparatus II method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty eight healthy male subjects, $23.25{\pm}1.43$ years in age and $64.82{\pm}6.77$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After two capsules containing 100 mg as acebrophylline were orally administered, blood was taken at predetermined time intervals and the concentrations of ambroxol in serum were determined using HPLC with electrochemical detector (ECD). The dissolution profiles of two formulations were similar at all dissolution media. In addition, the pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug Surfolase, were -1.64, -3.33 and -0.92% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 $(e.g., \;log\;0.93{\sim}log\;1.05\;and\;log\;0.88{\sim}log\;1.05$ for $AUC_t$, and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Burophil capsule was bioequivalent to Surfolase capsule.

• The Journal of Korean Obstetrics and Gynecology
• /
• v.23 no.1
• /
• pp.42-52
• /
• 2010

Purpose: This report aims to administer methodologic issues around recently conducted multicenter study for evaluating the effects of acupuncture on menopusal hot flashes and discuss practical issues for further implementation of acupuncture clinical trial for hot flashes. Methods: Study process were mentioned, and issues related to avoiding risk of bias, designing appropriate control group, optimal outcome measurement, potential different effects of menopausal status on study outcomes, and suggestions for developing future clinical trials are discussed. Results: Shortcomings of our multicenter study include lack of allocation concealment and assessor blinding, subjective outcome measurement, short-term follow-up, and fixed acupuncture regimen despite pragmatic purpose of this study. Improving trial design, using objective or validated outcomes, assessing long-term effects of acupuncture, and individualizing acupuncture regimen are needed in future clinical trials. Conclusion: We expect these practical discussions to enable researchers to plan and develop future well-designed clinical trials for evaluating the effects of acupuncture on hot flashes or other women's health issues.

• Journal of Dental Rehabilitation and Applied Science
• /
• v.32 no.2
• /
• pp.117-122
• /
• 2016

Purpose: Gingival whitening is one of dental treatment purposes which is close to treating aesthetic disorders. Initial gingival whitening treatment was done by dermabrasion using a high power Diode Laser. However, this treatment method cannot be free from any infection or pain after the treatment. Therefore, we have decided to progress gingival whitening treatment using a low power LED laser. Materials and Methods: The laser was irradiated on pork meat then the safety of output power, temperature change and skin denaturalization was measured. Bison 365 nm LED laser was irradiated on oral mucosal pigment of a 15 - 20 kg beagle for 15 min for 1 - 2 weeks, one or two times each. Any pigment loss was checked through Hematoxyline-Eosin staining. Results: The melanin pigments at the area of 365 nm LED Laser irradiation were decreased. Conclusion: The 365 nm LED Laser proposed in this study is considered to compensate the bleaching effect achieved by either using Diode laser or surgical methods.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
• /
• v.31 no.2
• /
• pp.40-59
• /
• 2018

Objectives : We report on the contents and reviews of the guidelines for clinical trials of herbal medicine for psoriasis. Methods : After reviewing the existing reports, the guidelines were drafted by the writing committee on guidelines for Korean medicine clinical trial center in Kyung Hee university Korean medicine hospital. Since then, the guidelines have been consulted by the experts in diseases, clinical trials and pharmaceuticals. In addition, the guidelines have been certified by the Korean medicine clinical trial center association and Korean Medicine Ophthalmology & Otolaryngology & Dermatology Society. Results : The guidelines for clinical trials are divided into 8 categories: (1) general contents, (2) evaluation standards of effectiveness, (3) outcome valuables, (4) selection of study participants, (5) designs of clinical trials, (6) safety evaluations, (7) combination therapies in psoriasis treatment and (8) Korean medical considerations. Conclusions : There are 3 major contents for discussion: (1) obscurity of Korean medical considerations to differentiate from existing guidelines, (2) the absence of Korean version of PASI and DLQI, which are validity parameters and (3) realistic institutional problem using the herbal medicine.

• Korean Journal of Clinical Pharmacy
• /
• v.21 no.4
• /
• pp.297-304
• /
• 2011

배경: 골다공증은 골대사의 불균형으로 인해 골 흡수가 골 형성보다 많아져 골밀도가 감소함으로서 발생한다. 골다공증의 이상적인 치료목표는 골형성을 증가시키거나 골소실을 방지하여 골량을 현 상태로 유지하는 것이다. 따라서 향후 발생되는 골소실을 에방하는 것이 골다공증의 원칙적이고 효과적인 치료방법이 될 것이다. 본 연구에서는 흑효모 중 $Aureobasidium$ $pullulans$으로부터 유래한 폴리칸(베타-글루칸)이 중년여성의 골대사에 미치는 영향을 규명하고자 하였다. 연구방법: 골대사에 대한 폴리칸의 효과를 규명하기 위해 12주간의 무작위배정, 이중눈가림, 플라세보 대조 임상연구를 수행하였다. 총 60명(폴리칸 투여군30명, 플라세보 투여군 30명)의 중년 여성 피험자가 등록되어 이 중 총 58명의 피험자가 최종적으로 12주간의 임상연구를 종료하였다. 결 과: 폴리칸(150 mg/d) 투여 12주 후, 폴리칸 투여군은 요 중 Deoxypyridinoline (DPD) 농도가 유의적인 감소를 보였다($P$=0.014). 혈청 중 Osteocalcin(OSC) 농도는 두 군 모두에서 유의적으로 증가하였으며, bone-specific alkaline posphatase (bALP) 와 collagen type 1 cross-linked C-telopeptide (CTx)는 유의적 변화가 보이지 않았다. 폴리칸은 골밀도(BMD)와 혈청 부갑상선 호르몬(iPTH)에 대해 유의적인 변화를 보이지 않았으나, 24시간 요 중 Ca 배설량은 폴리칸 투여군에서 유의하게 감소되었다($P$=0.028). 또한 폴리칸 투여군에서 고밀도지단백 콜레스테롤(HDL-cholesterol) 농도의 증가 경향 및 중성지방(triglyceride)의 유의적인 감소가 보였다. 임상연구 기간 중에 발생한 이상반응은 두 군간에 유의적인 차이를 보이지 않았다. 결 론: 본 연구에서는 폴리칸이 골대사 및 지질에 대해 일부 개선효과가 있음을 보여주었다. 그러나, 골다공증 예방 측면에서 보다 장기적인 임상연구와 피험자 수를 확대하여 골대사 및 지질대사에 대한 폴리칸의 예방적 효과를 규명할 필요가 있을것으로 사료된다.

• Bulletin of the Korean Chemical Society
• /
• v.34 no.8
• /
• pp.2425-2430
• /
• 2013

A simple, fast and robust analytical method was developed to determine imatinib in human plasma using liquid chromatography-tandem mass spectrometry with electrospray ionization in the positive ion mode. Imatinib and labeled internal standard were extracted from plasma with a simple protein precipitation. The chromatographic separation was performed using an isocratic elution of mobile phase involving 5.0 mM ammonium formate in water-5.0 mM ammonium formate in methanol (30:70, v/v) over 3.0 min on reversed-stationary phase. The detection was performed using a triple-quadrupole tandem mass spectrometer in multiple-reaction monitoring mode. The developed method was validated with lower limit of quantification of 10 ng/mL. The calibration curve was linear over 10-2000 ng/mL ($R^2$ > 0.99). The method validation parameters met the acceptance criteria. The spiked samples and standard solutions were stable under conditions for storage and handling. The reliable method was successfully applied to real sample analyses and thus a pharmacokinetic study in 27 healthy Korean male volunteers.

• Journal of Ginseng Research
• /
• v.46 no.4
• /
• pp.543-549
• /
• 2022

Background: In physical activity or labor, the human body is in a state of high intensity stress, and all parts or physiological functions of the body respond positively to maintain or balance the need for movement. The human body has many physiological changes in the process of movement, and fatigue is the external manifestation of various complex changes inside the human body. Fatigue is also a physiological mechanism of self-protection after the body reaches a certain level of activity, which can prevent the occurrence of life-threatening excessive functional failure. The generation of fatigue is a very complex process, and its mechanism has not been concluded yet. Therefore, it is an important work to search and screen the effective components of natural plants that have anti-fatigue effect and to explore their mechanism. Methods: This was a 8-week, randomized, double-blind, placebo-controlled clinical trial. A total of 110 subjects who passed physical examination were included according to the scheme design, and randomly divided into a test group which was given KRG and a placebo control group. The calculation is carried out according to the standard of sub-high-intensity exercise test. Results: There was no adverse effect on safety index of subjects after taking red ginseng capsule. After KRG treatment, subjective strength grade is significant lower than placebo treatment. Blood lactic acid content is significantly get lower after trial in KRG group, and significant lower than placebo group. Creatine phosphokinase(CK) content is significantly get lower after trial in KRG group, and significant lower than placebo group. Conclusion: According to the criterion in the test scheme, the result shows that KRG is helpful on relieving physical fatigue.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.32 no.4
• /
• pp.291-297
• /
• 2018

The purpose of pilot clinical trial is to evaluate the efiicacy and safety of Needle-Embedding acupuncture therapy on TEWL(Transepidermal Water Loss) and Skin hydration. A total of 24 human who visited Dongshin Oriental Medical Center from December 1st, 2016 to July 31st, 2017 were included in the pilot clinical trial. Needle-Embedding acupuncture therapy performed at Gokji(LI11). We observed change of TEWL(Transepidermal Water Loss), Skin hydration before and after Needle-Embedding acupuncture therapy. In the primary endpoint, index of TEWL showed a statistically insignificant decline ($8.5{\pm}2.12{\rightarrow}7.8{\pm}1.53g/h/m^2$). Index of skin hydration showed a statistically significant result ($38.2{\pm}6.77{\rightarrow}36.8{\pm}6.64$). To evaluate the safety, Adverse events and Vital sign check were conducted and there were no problem. And when the physical response, self-awareness, skin system, musculoskeletal pain, and other abnormal responses were assessed 60 minutes and 24 hours and 7 days after Needle-Embedding acupuncture therapy at Gokji(LI11) for stability assessment, Adverse events disappeared during a pilot clinical trial. According to the above pilot clinical trial, it is suggested Needle-Embedding acupuncture therapy were effective for Skin moisturizing and safe.