Flip-Flop Kinetics of Collagen Tripeptide (Gly-Pro-Hyp) and Dipeptides (Gly-Pro and Pro-Hyp) in Rats

Hee-Chul Chung,Wonku Kang(강원구) 한국식품영양과학회 2020 한국식품영양과학회 학술대회발표집 Vol.2020 No.10

국내 의약품 임상시험 실시기관에서의 임상시험 관리약국 운용 현황

장유정 ( Yoo Jeong Jang ),강원구 ( Wonku Kang ),이주미 ( Joomi Lee ),이혜원 ( Hae Won Lee ),박민수 ( Min Soo Park ),윤영란 ( Young Ran Yoon ) 영남대학교 약품개발연구소 2013 영남대학교 약품개발연구소 연구업적집 Vol.23 No.0

Background: There is a lack of research on the status of clinical trial pharmacy and clinical trial pharmacist (CTP) in Korea. This study was aimed to investigate the current status of clinical trial pharmacy and clinical trial pharmacists. Methods: The survey was performed using the 41-item questionnaire designed to investigate information on the following; (1) current status of clinical trial pharmacy designated by Korea Food and Drug Administration, (2) current status of working condition, management, and satisfaction index of CTP. Data collected was analyzed by t-test and χ². Results: Among the CTPs who responded, 92.7 % belonged to department of pharmacy, and 7.3 % to clinical trial center. 90.2 % of the respondents were women. Forty-two point seven percents of the respondents had more than 3 years of experience in the clinical trial field. 36.6 % answered that the current number of CTPs in the institution was ‘2’. Sixty-three point four percents answered that they subsumed an additional post. Regarding the question on “whether the equipment and working environment of your clinical trials pharmacy is adequate”, 65.1 % of the respondents answered as ‘Inadequate’. Ninety-eight point eight percents answered that work-related education is needed. Ninety-three point nine percents answered that the quality of clinical trials is related to the improvement of the working environment of CTP. Conclusion: Clinical trial pharmacy`s facility and number of actually working CTP were insufficient. Proper and continuous education and training for CTPs are needed to improve the quality of clinical trials conducted in Korea, with strong institution support and timely regulation change.

유럽의 규제과학 및 규제과학 인재양성 프로젝트

신호철,박재홍,김지원,백다정,이윤지,정선영,강원구,김하형,최영욱,김은영,Shin, Hocheol,Park, Jaehong,Kim, Jiwon,Baek, Dajung,Lee, Yun-ji,Jung, Sun-Young,Kang, Wonku,Kim, Hahyung,Choi, Young Wook,Kim, Eunyoung 한국임상약학회 2021 한국임상약학회지 Vol.31 No.3

Background: Need for regulatory science is emerging with the development of pharmaceutical industry. It is essential to train regulatory science experts to meet the needs of technology and regulations to evaluate advanced products. Major regulatory science countries are conducting the regulatory science activities and fostering the experts. Methods: Published literature and the relevant website of European Union (EU) were reviewed and criteria were developed. In particular, we focused on in depth descriptions of the Innovative Medicines Initiative program, which was conducted twice. Results: EU is striving to provide funding and training experts for the development of the regulatory science by horizon 2020 and regulatory science to 2025. Innovative medicines initiative (IMI) is a public-private partnership aimed at the development of the pharmaceutical industry, including the regulatory science. IMI education and training projects have provided various education and training course including short-term curriculum and master and doctoral course. The difference between South Korea's regulatory science expert training project in 2021 and the EU's IMI education and training projects is participation of pharmaceutical companies. While the pharmaceutical companies participate in the IMI project to select project topics and form a community, South Korea's project is focused on the Ministry of Food and Drug Safety and universities. Conclusion: Through successful active networks with regulatory party, pharmaceutical companies, and universities, a great innovative advance of regulatory science in South Korea is expected.

Atorvastain과 Telmisartan의 약물상호작용

박진남 ( Jinhyun Park ),노금한 ( Keumhan Noh ),임미선 ( Misun Lim ),강원구 ( Wonku Kang ) 영남대학교 약품개발연구소 2014 영남대학교 약품개발연구소 연구업적집 Vol.24 No.0

Purpose: Atorvastatin, a HMG-CoA reductase inhibitor is widely prescribed in hyperlipidemic patients and telmisartan,an angiotensin receptor blocker is frequently used in the treatment of hypertension. Both drugs are substrates of organicanion transporting polypeptide (OATP) expressed in basolateral membrane in the liver, and undergo high first passmetabolism. Therefore, OATP-mediated hepatic uptake is important for disposition and metabolism of these drugs. Thepresent study was designed to investigate the pharmacokinetic interactions between atorvastatin and telmisartan in rats. Method: Young adult SD rats were divided into three groups (n=6, each) and atorvastatin (10 mg/kg) and telmisartan(4 mg/kg) were orally given alone and together. Heparinized blood was serially taken and plasma concentrations of bothdrugs were measured using HPLC-MS/MS. Pharmacokinetic parameters of two drugs were calculated. Results: No significantpharmacokinetic change was found except a delay of time to peak of telmisartan when administered with atorvastatin. Each drug at the present dosage seemed to be insufficient to alter the pharmacokinetic parameters of itscounterpart drug. Conclusion: Conclusively, co-administration of atorvastatin and telmisartan may lead to negligibleclinical consequences.

폐질환 치료제의 효율적인 신약개발을 위한 생체표지자 및 대리결과 변수

서정원(Jeong-Won Seo),이병요(Byung-Yo Lee),채정우(Jung-Woo Chae),손추영(Chu-Young Son),강원구(Wonku Kang),채한정(Han-Jung Chae),권광일(Kwang-il Kwon) 대한약학회 2010 약학회지 Vol.54 No.2

Biomarkers are likely to be important in the study of various pulmonary diseases for many reasons. Research efforts in developing biomarkers and surrogate endpoints of lung diseases have resulted in the identification of new risk factors and novel drug targets, as well as the establishment of treatment guidelines. Government agencies, academic research institutions, diagnostic industries, and pharmaceutical companies all recognize the importance of biomarkers in new drug development and advancing therapies to improve public health. In drug development, biomarkers are used to evaluate early signals of efficacy and safety, to select dose, and to identify the target population. Identification of suitable end points not only would help investigators design appropriate clinical trials but would assist clinicians in caring for this patient population. Though the area of pulmonology has received much attention in the past decades, it still lags behind with regard to the development of biomarkers, particularly those of health effects and susceptibility. This review critically summarized several biomarker researches such as Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study with objectives of identifying the parameters that predict disease progression of COPD, as well as biomarkers that may serve as surrogate end-points.

Ebastine의 약동화에 미치는 Telmisartan의 영향

백상훈 ( Sanghoon Baek ),박선경 ( Sunkyoung Park ),장유정 ( Yoo Jeong Jang ),임미선 ( Misun Lim ),강원구 ( Wonku Kang ) 영남대학교 약품개발연구소 2014 영남대학교 약품개발연구소 연구업적집 Vol.24 No.0

Purpose: Telmisartan, an angiotensin receptor blocker has been known to be a potent blocker of both CYP2J2 and Pglycoprotein(P-gp) in vitro. This study aims to investigate the drug-drug interactions between telmisartan and ebastine,a CYP2J2 and P-gp substrate in rats. Method: Ebastine (10 mg/kg) was orally given in the presence and absence oftelmisartan (4 mg/kg, p.o.). Heparinized blood was serially taken and the plasma concentrations of ebastine and its threemetabolites (hydroxyebastine, carebastine and desalkylebastine) were determined using LC-MS/MS, and their pharmacokineticparameters were compared. Results: Peak concentrations (Cmax) and AUC of ebastine were significantly (p<0.05)increased in the presence of telmisartan by 2.1 and 1.9 times, respectively. While Cmax of hydroxyebastine was significantlyincreased by 1.9 times, the half-life of hydroxyebasteine was decreased significantly with telmisartan (p<0.05). There was no change in the pharmacokinetic parameters of carebastine, the active metabolite of ebastine, and desalkylebastinewas not detected in plasma. The systemic exposure of ebastine was significantly augmented by telmisartan, indicatingthat telmisartan may enhance the absorption of ebastine by blocking P-gp. Conclusion: Although telmisartanmay also partially contribute to inhibit the biotransformation to hydroxyebastine, the inhibitory action seemed to beoverridden by the enhancement of absorption, because the generation of hydroxyebastine was not diminished. In spiteof such interactions between telmisartan and ebastine, no clinical consequence could be expected due to no significantchange of the active metabolite, carebastine.

Efavirenz, indinavir, lopinavir, ritonavir의 LC-MS/MS를 이용한 동시 정량법

채정우,배경진,백인환,서정원,이병요,이은주,남진경,강원구,권광일 충남대학교 약학대학 의약품개발연구소 2009 藥學論文集 Vol.24 No.-

Efavirenz indinavir and kaleta (co-formulation of lopinavir and ritonavir) are important antiretroviral drugs which have been proved to be human immunodeficiency virus (HIV) protease inhibitors and reduced the morbidity and mortality associated with HIV-1 infection. A brief and fast high performance liquid chromatography coupled with electrospray mass spectrometry (LC-MS/MS, API 4000) method for the determination of 4 anti-retroviral agents (efavirenz, lopinavir, indinavir, ritonavir) in human plasma was developed and validated. A simple protein precipitation method was used on 100μl of human plasma. And internal standard solution (10 ng/ml methaqualone) 1ml and reconstitution solution (MeOH) 1ml were added. After vortexing for 30 s and centrifuging at 13,200rpm for 10min, 2μl of supernatant was injected into the column (XTerra MS C_(18) column, 2.1mm × 50mm 3.5㎛ particle size). The mobile phase consisted of MeOH and 0.1% formic acid in water (80:20 , v/v). The chromatogram was run for 1.5 min at a flow rate of 300μl/min. A triple quadrupole mass spectrometer was operated in a positive ion mode (lopinavir, indinavir, ritonavir) and negative mode (efavirenz), simultaneously and multiple reaction monitoring (MRM) was used for drug quantification. The precursor-to-product ion transitions of m/z 316→69 (efavirenz) and 629→447 (lopinavir) and 614→421 (indinavir) and 721→296 (ritonavir)were used to measure and quantify the analyte. The limit of quantitation (LOQ) was 50 ng/ml (efavirenz, indinavir, ritonavir) and 100 ng/ml (lopinavir). The weighted (l/y²) calibration curve was linear over human plasma range 50∼5000ng/ml (efavirenz), 100∼20000ng/ml (lopinavir), 50∼10000ng/ml (indinavir), 50∼2000ng/ml (ritonavir), correlation coefficient(r²) of 4 antiretroviral agents were higher than 0.998. Accuracies and intra-run precisions ranged within 86.60 and 113.29%, 1.06 and 11.16% for all 4 drugs analysed. This analytical method used to determine these drugs was fast and easy to perform, with minimal sample preparation, and without compromising precision and accuracy. The developed method was successful to determine antiretroviral agents in human plasma, and proved suitable for clinical pharmacokinetic study.