• Biomolecules & Therapeutics
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• v.25 no.3
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• pp.288-295
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• 2017

The incidence of polypharmacy-which can result in drug-drug interactions-has increased in recent years. Drug-metabolizing enzymes and drug transporters are important polypharmacy modulators. In this study, the effects of bosentan and rifampin on the expression and activities of organic anion-transporting peptide (OATP) and cytochrome P450 (CYP450) 2C9 and CYP3A4 were investigated in vitro. HEK293 cells and primary human hepatocytes overexpressing the target genes were treated with bosentan and various concentrations of rifampin, which decreased the uptake activities of OATP transporters in a dose-dependent manner. In primary human hepatocytes, CYP2C9 and CYP3A4 gene expression and activities decreased upon treatment with $20{\mu}M$ $bosentan+200{\mu}M$ rifampin. Rifampin also reduced gene expression of OATP1B1, OATP1B3, and OATP2B1 transporter, and inhibited bosentan influx in human hepatocytes at increasing concentrations. These results confirm rifampin- and bosentan-induced interactions between OATP transporters and CYP450.

• Bulletin of the Korean Chemical Society
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• v.35 no.1
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• pp.250-252
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• 2014

Lipoprotein-associated phospholipase A2 (Lp-$PLA_2$) is a crucial enzyme in atherosclerosis as a potential drug target. The most remarkable Lp-$PLA_2$ inhibitory drug is Darapladib. We determined the binding pose of Darapladib to Lp-$PLA_2$ through docking study. Darapladib formed two hydrogen bonding interactions with the side chain of Tyr160 and Gln352 and several pi-pi interactions with aromatic and aliphatic hydrophobic residues of Lp-$PLA_2$. It is known that the dietylpropan-amine moiety of Darapladib has influence on the improvement of its oral bioavailability and we supposed this in our docking results.

• Korean Journal of Clinical Pharmacy
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• v.30 no.1
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• pp.44-50
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• 2020

Background: Drug-drug interactions (DDIs) in patients using oral anticancer treatment are more common than in those using injectable anticancer agents. In addition, DDIs related to anticancer treatment are known to cause clinically significant outcomes, such as treatment failure and severe toxicity. To prevent these negative outcomes, significant DDIs are monitored and managed using the information provided in drug databases. We aimed to evaluate the consistency of information on clinically significant DDIs for tyrosine kinase inhibitors (TKIs) between representative drug databases. Methods: We selected clinically significant DDIs involving medications that are co-prescribed with TKIs and met the following criteria: the severity level of DDIs was equal or greater than "D" in Lexicomp^® or "major" in Micromedex^®. We then analyzed the consistency of the severity classification and evidence level between the drug databases. Spearman's correlation coefficient was used to identify the relationship between DDI information in the drug databases. Results: In total, 627 DDI pairs were identified as clinically significant; information on these was provided by Lexicomp^® and Micromedex^® for 571 and 438 pairs, respectively, and both drug databases provided information on 382 DDI pairs. There was no correlation between the severity and evidence level of DDIs provided in the two databases; Spearman's correlation coefficient for Lexicomp^® and Micromedex^® was -0.009 (p=0.861) and -0.064 (p=0.209), respectively. Conclusion: To judge the significance of DDIs, healthcare providers should consider that the information on DDIs may be different between drug information databases; hence, clinical factors must be considered concurrently.

• Archives of Pharmacal Research
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• v.25 no.4
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• pp.397-415
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• 2002

This paper deals with a crucial mechanism for interaction of basic drugs and cardiac glycosides at the hepatic uptake level. Available literature data is provided and new material is presented to picture the differential transport inhibition of bulky (type2) cationic drugs by a number of cardiac glycosides in rat liver. It is shown that the so called organic anion transporting peptide 2 (oatp2) is the likely interaction site: differential inhibition patterns as observed in oocytes expressing oatp2, could be clearly identified also in isolated rat hepatocytes, isolated perfused rat liver and the rat in vivo. The anticipation of transport interactions at the hepatic clearance level should be based on data on the relative affinities of interacting substrates for the transport systems involved along with knowledge on the pharmacokinetics of these agents as well as the chosen dose regimen in the studied species. This review highlights the importance of multispecific tranporter systems such as OATP, accommodating a broad spectrum of organic compounds of various charge, implying potential transport interactions that can affect body distribution and organ clearance.

• Journal of Integrative Natural Science
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• v.4 no.1
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• pp.23-30
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• 2011

Multidrug resistance (MDR) is one of the main obstacles in the chemotherapy of cancer. MDR is associated with the over expression of P-glycoprotein (P-gp), resulting in increased efflux of chemotherapy from cancer cells. Inhibiting P-gp as a method to reverse MDR in cancer patients has been studied extensively, but the results have generally been disappointing. First-generation agents were limited by unacceptable toxicity, whereas second-generation agents had better tolerability but were confounded by unpredictable pharmacokinetic interactions and interactions with other transporter proteins. Third-generation inhibitors have high potency and specificity for P-gp. Furthermore, pharmacokinetic studies to date have shown no appreciable impact on drug metabolism and no clinically significant drug interactions with common chemotherapy agents. Third-generation P-gp inhibitors have shown promise in clinical trials. The continued development of these agents may establish the true therapeutic potential of P-gp-mediated MDR reversal.

• Journal of Microbiology and Biotechnology
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• v.26 no.2
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• pp.213-225
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• 2016

To reduce attrition in drug development, it is crucial to consider the development and implementation of translational phenotypic assays as well as decipher diverse molecular mechanisms of action for new molecular entities. High-throughput fluorescence and confocal microscopes with advanced analysis software have simplified the simultaneous identification and quantification of various cellular processes through what is now referred to as high-content screening (HCS). HCS permits automated identification of modifiers of accessible and biologically relevant targets and can thus be used to detect gene interactions or identify toxic pathways of drug candidates to improve drug discovery and development processes. In this review, we summarize several HCS-compatible, biochemical, and molecular biology-driven assays, including immunohistochemistry, RNAi, reporter gene assay, CRISPR-Cas9 system, and protein-protein interactions to assess a variety of cellular processes, including proliferation, morphological changes, protein expression, localization, post-translational modifications, and protein-protein interactions. These cell-based assay methods can be applied to not only 2D cell culture but also 3D cell culture systems in a high-throughput manner.

• Korean Journal of Clinical Pharmacy
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• v.23 no.4
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• pp.334-343
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• 2013

Purpose: This study aims to investigate consumers' demand of and perspective on drug information domestically available and uncover hurdles that they faced while utilizing information. Methods: We conducted a survey of 101 consumers, face-to-face after obtaining informed consent. Chi-squared, or Fisher's exact tests, and multivariate logistic models were used to investigate the association between participants' perceptions and characteristics. Results: As results, participants showed the highest demand for "Adverse effects >90%"; "Drug interactions/Dosage/Drug-food interactions/Indication >80%", and utilized package inserts (52%), doctors (41%) and pharmacists (36%) most often as information sources. Generally, the most common difficulty consumers suffered with was that "it is hard to understand (51%)". With public sources of drug information, sixty one percent of participants were "unaware of the provision of information", resulting in strikingly low usage rates (5~11%). Subgroup analyses indicated that the older (${\geq}50$ years) and the disadvantaged might have been placed in the blind spot of information mostly developed online (p<0.05).Conclusion: In conclusion, public sources of drug information that have been developed online might fail to meet consumers' demand. Greater efforts should be made to balance the development of the information sources between online and offline, and to increase accessibility of the established information sources.

• Korean Journal of Pharmacognosy
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• v.25 no.1
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• pp.1-10
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• 1994

The screening of 150 Chinese drugs which are most frequently prescribed in Korean traditional medicine showed that at least 30% of the drugs affected barbiturate-induced hypnosis. This effect was mainly attributable to the alteration of drug metabolism. Phytochemical works resulted in the isolation of furanocoumarins, lignans, sesquiterpenes and saponins as drug metabolism modifiers. The structure-activity relationship is discussed.

• Journal of Korean Institute of Industrial Engineers
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• v.39 no.1
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• pp.20-29
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• 2013

Medical errors such as adverse drug event, improper transfusion, wrong-site surgery, mistaken patient identity and so on commonly occur at health care practice. Information technology, like Drug Utilization Review(DUR) system which reviews, analyzes, and interprets medication data when prescribing, can play a key role in reducing such medical errors and improving patient safety. Korean Government has guided all hospitals to implement concurrent DUR(cDUR) system, which is the first case worldwide in that all healthcare providers have to use cDUR system when prescribing. This paper introduced a case study that a tertiary hospital has integrated the cDUR system into its comprehensive Hospital Information System(HIS) and analyzed the whole prescription data during a week right after adoption of cDUR system. Considering technical strength and weakness, the cDUR system was integrated into the HIS, using Broker Servers for minimizing doctors' anxiety. As the quantitative analysis of the whole prescription data, DUR conflict events, which mainly included duplicate medications and contra-indicated drug interactions for outpatients, were 2.77%. Although only 0.7% is for the contra-indicated drug interactions, it will be greatly devoted to achieve the purpose of DUR such as improving patient safety.

• Archives of Pharmacal Research
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• v.4 no.2
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• pp.99-107
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• 1981

To investigate the protein binding characteristics of ibuprofenlysine, the effects of drub conentration, pH, ionic strength and protein concentration on the binding of drug to protein concentration on the binding of drug to protein were studied by fluorescence probe method. The conformational change of protein was investigated by circular dichroism (CD) measurement. As the concentration of drug increases, the association constant decreases. These may be due to complex formation of the probe and drug, or the interaction of the protein-probe complex and drug. The association constant for ibuprofenlysine increased with increasing protein concentration. These finding suggest a sharing of one ibuprofenlysine molecule by more than one protein molecule in the binding. The binding between ibuprofenlysine and protein was dependent on pH and ionic strength. It seems that both hydrophobic binding and some electrostatic forces are involved in the binding of ibuprofenlysing to protein.