• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.86-87
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• 2002

Recent technological innovations in the drug discovery process such as combinatorial synthesis and high throughput screening have led to the identification of an increasingly large number of compounds at the hits-to-leads stage. Therefore, rapid and precise pharmacokinetic/metabolic screening is essential to enhance the tractability of selected leads and to minimize the risk of failure in the later stages of drug development. (omitted)

• 한국식품위생안전성학회지
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• 제30권3호
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• pp.289-294
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• 2015

본 연구에서는 건강기능성 식품원료로서 이용 빈도가 증가하고 있는 하수오, 백수오 및 이엽우피소에 대한 종 특이 프라이머를 개발하였다. 개발된 종 특이 프라이머는 하수오, 백수오 및 이엽우피소에 대해 원물뿐만 아니라 육안 확인이 어려운 가공식품 등을 대상으로 사용원료의 진위여부를 빠르고 정확하게 확인할 수 있었다. 따라서 본 연구에서 개발한 종 특이 PCR방법은 기존의 일반 프라이머를 사용하는 방법이 가지고 있는 식품 적용 한계를 극복할 수 있을 것이라고 판단하였다.

• Journal of Pharmaceutical Investigation
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• 제34권3호
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• pp.161-168
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• 2004

5-Fluorouracil (5-FU) is an antimetabolite anticancer agent active against many types of solid tumors. Tegafur (TF), a prodrug of 5-FU, is frequently used in combination with uracil as dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine. We studied the stability of 5-FU and TF in biological fluids of rats and determined their bioavailability (BA) and excretion into bile, and urine. The drug concentrations were analyzed by an HPLC method. At room temperature, there was a 14-30% decrease in the concentration of 5-FU and TF in bile, urine, and plasma specimen at 10 and $100\;{\mu}g/ml$ over 240 min. No significant difference was noted among the sample types or between two different concentrations of 10 and $100{\mu}g/ml$. The decrease in drug concentration was significantly less in samples kept on ice (6-12%) for both drugs. These data indicate that biological fluid samples containing 5-FU or TF in plasma, urine, or bile should be placed on ice during the sample collection. Following these storage guidelines, samples were collected after administration 50 mg/kg of each drug via i.v. or oral route. BA was 1.5 folds greater for TF (60%) than that of 5-FU (42%). Approximately 0.52 and 3.3% of the i.v. doses of 5-FU and TF was excreted into bile, respectively. Renal clearance of 5-FU was about 16% of its total body clearance. These results suggest that instability of 5-FU and TF in biological fluids should be considered in pharmacokinetic or pharmacogenomic studies.

• Genomics & Informatics
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• 제16권3호
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• pp.52-58
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• 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.

• 지식경영연구
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• 제19권3호
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• pp.189-223
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• 2018

This paper examined the effect of innovation networks comprising research and development (R&D) collaboration on innovation performance of Korean pharmaceutical firms. As co-assigned patents and co-affiliated publications are common technical outcomes of successful R&D collaboration in the pharmaceutical industry, social network analysis technique was applied for analyzing innovation networks through patent and publication data. Results of Social network analysis indicated that a small set of highly innovative firms in the Korean pharmaceutical industry were actively involved in patenting and publishing. And the analysis of structural equation model found the followings: (1) R&D intensity significantly affected patenting, publication and new drug development, (2) the activity of patenting and publishing was positively related with the innovation performance measured by new drug development, and (3) R&D collaboration in terms of degree centrality of co-patent network played significant moderating roles on the relationships among R&D intensity, patenting, and new drug development. These findings are expected to be helpful to researchers as well as policy-makers to devise innovation-promoting policies in the Korean pharmaceutical industry. Discussions and limitations of the study are provided in the last part.

• Bulletin of the Korean Chemical Society
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• 제34권8호
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• pp.2466-2472
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• 2013

Human immunodeficiency virus type-1 (HIV-1) is a causative agent of Acquired immunodeficiency syndrome (AIDS), which has affected a large population of the world. Viral envelope glycoprotein (gp120) is an intrinsic protein for HIV-1 to enter into human host cells. Molecular docking guided molecular dynamics (MD) simulation was performed to explore the interaction mechanism of heterobiaryl derivative with gp120. MD simulation result of inhibitor-gp120 complex demonstrated stability. Our MD simulation results are consistent with most of the previous mutational and modeling studies. Inhibitor has an interaction with the CD4 binding region. Van der Waals interaction between inhibitor and Val255, Thr257, Asn425, Met426 and Trp427 were important. This preliminary MD model could be useful in exploiting heterobiaryl-gp120 interaction in greater detail, and will likely to shed lights for further utilization in the development of more potent inhibitors.

• Journal of Pharmaceutical Investigation
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• 제41권2호
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• pp.103-109
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• 2011

The objective of the study was to prepare self-microeulsifying drug delivery system (SMEDDS) incorporating atorvastatin calcium and evaluate its properties and oral bioavailability. Solubility of atorvastatin in various vehicles was determined. Pseudo-ternary phase diagrams were constructed to identify the good self-emulsification region. The droplet size distributions of the resultant emulsions were determined by dynamic light scattering measurement. The mean droplet size of chosen formulation (20% ethyl oleate, 40% tween-80, 40% Carbitol$^{(R)}$) was $23.4{\pm}1.3$ nm. The SMEDDS incorporating atorvastatin calcium appeared to be associated with better performance in dissolution and pharmacokinetic studies, compared with raw atorvastatin calcium. In dissolution test, the release percentage of atorvastatin from SMEDDS mixture could rapidly reach more than 95% within 3 min. Oral $AUC_{0{\rightarrow}8hr}$ values in SD rats was $1994{\pm}335\;ng{\cdot}hr/mL$, which significantly increased (P<0.05) compared with raw atorvastatin calcium. The SMEDDS formulation was relatively stable when stored at $4^{\circ}C$ during 3 months. Our studies illustrated the potential use of SMEDDS for the delivery of hydrophobic compounds, such as atorvastatin, by the oral route.

• 동의생리병리학회지
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• 제21권1호
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• pp.235-242
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• 2007

The effects of Jujubae Fructus and Licorice extracts on the main components of Sijotang Euphorbiae Kansui Radix, Daphinis Genkwa Flos, Euphonrbiae Pekinensis Radix (KWD) treatment [KWD decoction (KWDD) and KWD powder (KWDP)] related toxicities were examined in the kidney and the liver. To select more suitable extract which effectively reduce KWD-treatment related toxicities in the body, blood biochemical and histopathological changes induced by KWD were analyzed in the rats which received treament of KWD + Jujubae Fructus or KWD + Licorice. In the present study, no KWD-treatment related blood biochemical and histopathological change in the liver was detected. However, increase of tubules containing hyaline casts and atrophic tubules in the kidney was detected as the indicators of KWDD treatment related nephrotoxicity. Addition of Jujubae Fructus (KWDDJ) or Licorice (KWDDL) extracts effectively inhibited the nephrotoxcity induced by KWDD treatments. More ameliorated effects were acquired by addition of Jujubae Fructus extract (KWDDJ) than Licorice (KWDDL). In KWDP treatment, there was no significant difference in the number of tubules containing hyaline casts in all drug treated groups compared to normal or control group except for high dose of KWDP. Both of Jujubae Fructurs and Licorice reduced high dose of KWDP treatment related nephrotoxicity, and there was no significant difference between KWDPJs and KWDPLs. It is concluded that addition of Jujubae Fructus is more suitable than Licorice in reducing the nephrotoxicty of KWDD, also it is more suitable to taking Sipjotang in the form of powder than decoction.

• Journal of Microbiology and Biotechnology
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• 제16권8호
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• pp.1311-1315
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• 2006

Aminocyclitol antibiotic validamycin A, a prime control agent for sheath blight disease of rice plants, is biosynthesized by Streptomyces hygroscopicus var. limoneus. Within the validamycin biosynthetic gene cluster, vldBC forms an operon of vldABC with vidA, the gene encoding 2-epi-5-epi-valiolone synthase. Biochemical studies, employing the recombinant proteins from Escherichia coli, established VldB and VldC as D-glucose $\alpha$-1-phosphate uridylyltransferase and glucokinase, respectively. This finding substantiates that the validamycin biosynthetic gene cluster harbors genes encoding the enzymes for UDP-glucose formation from glucose. Therefore, we propose that validamycin biosynthesis employs its own catalysts to generate UDP-glucose, but not depending on the primary metabolism.

• Journal of Microbiology and Biotechnology
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• 제17권6호
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• pp.1045-1048
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• 2007

Two genes, dps encoding decaprenyl diphosphate synthase and dxs encoding 1-deoxy-D-xylulose 5-phosphate synthase, were isolated from Rhizobium radiobacter ATCC 4718. DNA sequencing analysis of the dps and dxs genes revealed an open reading frame of 1,077 bp and 1,920 bp, respectively. The heterologous expression in Escherichia coli BL21(DE3) was carried out in order to identify their functions. Recombinant E. coli BL21(DE3) harboring the dps gene produced $CoQ_{10}$ as well as $CoQ_8$ and $CoQ_9$, whereas E. coli harboring only the dxs gene produced more $CoQ_8$ compared with the wild-type E. coli. Additionally, the coexpression of dps and dxs genes in E. coli was carried out. The recombinant E. coli harboring only the dps gene produced $0.21{\pm}0.04\;mg/l$ of $CoQ_{10}$, whereas the coexpressed E. coli with dps and dxs genes produced $0.37{\pm}0.07\;mg/l$ of $CoQ_{10}$. HPLC analysis also showed that the $CoQ_{10}$ fraction (100% of the total CoQs distribution) was increased from $15.86{\pm}0.66%$ (only dps) to $29.78{\pm}1.80%$ (dps and dxs).