• Korean Journal of Clinical Pharmacy
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• v.19 no.1
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• pp.1-17
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• 2009

Adverse drug reactions (ADR) caused by inappropriate prescription are responsible for major socioeconomic loss. Drug-drug interactions (DDI) has been recognized as a major part of ADRs and, therefore, healthcare professionals should prevent possible DDIs to minimize preventable ADRs. This study aimed to examine DDI information in drug information references and Korea Food & Drug Administration (KFDA) drug labeling information. Drug ingredients from the formulary of Health Insurance Review and Assessment Service in Korea (HIRA) were included for the study. DDI information source used for the study were Micromedex Drugdex and Drug Information Facts (DIF) with the DDI severity level of "moderate" or more. The DDI information in KFDA drug labeling were collected and compared. Drug ingredients were classified with KFDA Drug Classification and ATC Classification of WHO for the analysis. Among the total 1,355 drug ingredients satisfying inclusion criteria, 738 ingredients involved at least one DDI, which was described in Micromedex and/or DIF. Drug Ingredients of 176 involved DDI only described in KFDA drug labeling, but not Micromedex nor DIF. Drug ingredients of 35 which DDIs were described in Micromedex or DIF did not have DDI based on KFDA drug labeling. Micromedex and DIF retrieved 7,582 and 3,071 DDIs, respectively 57.6% and 58.5% of DDIs were also described in KFDA drug labeling. Central nervous system (CNS) drugs, cardiovascular system (CVS) drugs and the antiinfectives appeared to have higher frequency of DDIs among all drug classes. The highest number of DDIs with high severity level ("contraindicated" or "major") were the DDIs of CNS drugs. The antiinfectives are the second drug group having serious DDIs. The DDI pairs of the CNS drug and the antiinfective had the highest contraindication risk (13.6%). DDI information from Micromedex and DIF were not consistent with the result that only 465 ingredients' DDIs are common in both literature (total DDI numbers were 715 vs 488, respectively). And 1,652 DDI information are common in both references among 7,582 vs 3,071 DDIs, respectively. Only 55.2% of DDI information in the database contained in the KFDA drug labeling. Prescribers and pharmacists should pay attention to the drugs for CV system, CNS and infections because of higher risk of possible DDIs compared to other drug classes. KFDA drug labeling is not likely to be recommended as a good information source for DDI due to significant inconsistency of information. Drug information providers should be aware that DDI information from different sources are not consistent and therefore multiple references should be used.

• YAKHAK HOEJI
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• v.47 no.6
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• pp.382-389
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• 2003

This study has collected prescriptions of individual chronic outpatients in an army hospital, analysed them, and investigated the possible drug interactions. It also reviewed the mechanism of drug interactions. Out of total of 42 outpatients with chronic diseases, the percentages of populations having hypertension, hypertension with diabetes, uncomplicated diabetes, hyperlipidemia, hypertension with cardiac insufficiency, and ventricular septal defect were 62%, 19%, 10%, 5%, 2%, and 2%, in the corresponding order. The average number medications prescribed for the outpatients were 2.5 with the highest frequency of five medications in two patients. The number of drug-drug interactions detected was 456 prescriptions out of total of 1104 prescriptions during the study period, accounting for 41.3%. The most frequent drug-drug interaction was between beta-blockers and calcium channel blockers with 132 prescriptions followed by one between beta-blockers and cimetidine with 89 prescriptions. Based on the high incidence of possibly dangerous drug interactions, much attention needs to be aid to the drug-drug interactions in the pharmacotherapy for the treatment of outpatients with chronic diseases in army hospital setting.

• Journal of Pharmaceutical Investigation
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• v.24 no.4
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• pp.289-295
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• 1994

Pharmacokinetic drug interaction between phenytoin and verapamil was investigated following i.v. administration of two drugs concomitantly to rabbits. Verapamil was coadministered with phenytoin (5 mg/kg) to rabbits at the doses of 0.5,1 and 2 mg/kg, respectively. Plasma concentration and AUC of phenytoin were increased significantly, but volume of distribution and total body clearance were decreased significantly (p<0.05) at doses of 1mg and 2mg/kg of verapamil, respectively. From the results of this experiment, it is desirable that dosage regimen of phenytoin should be adjusted and that therapeutic drug monitoring should be performed for reduction of side or toxic effect when phenytoin should be administered with verapamil in clinical practice.

• Archives of Pharmacal Research
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• v.27 no.11
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• pp.1161-1167
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• 2004

Adriblastina, a cancerostatic anthracycline antibiotic, causes considerable oxidative damage to DNA molecules. The interaction of this compound with DNA was investigated using Osteryoung square wave stripping voltammetry (OSWSV) and cyclic voltammetry (CV) at an in situ mercury film electrode. It was found that the equilibrium constant of the bonded oxidized form of the drug was 63 times bigger more important than that of the bonded reduced form. Copper forms 1 metal: 2 drug stoichiometry complex which is highly stable compared to ssDNA-drug interaction and consequently inhibited the drug biochemical damaging effects. Copper complex offered sub-nanogram determination of adriblastina in aqueous and urine media.

• Mass Spectrometry Letters
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• v.7 no.4
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• pp.106-110
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• 2016

Ginseng, a traditional herbal drug, has been used in Eastern Asia for more than 2000 years. Various ginsenosides, which are the major bioactive components of ginseng products, have been shown to exert numerous beneficial effects on the human body when co-administered with drugs. However, this may give rise to ginsenoside-drug interactions, which is an important research consideration. In this study, acassette assay was performed the inhibitory effects of 12 ginsenosides on seven cytochrome P450 (CYP) isoforms in human liver microsomes (HLMs) using LC-MS/MS to predict the herb-drug interaction. After incubation of the 12 ginsenosides with seven cocktail CYP probes, the generated specific metabolites were quantified by LC-MS/MS to determine their activities. Ginsenoside Rb1 and F2 showed strong selective inhibitory effect on CYP2C9-catalyzed diclofenac 4'-hydroxylation and CYP2B6-catalyzed bupropion hydroxylation, respectively. Ginsenosides Rd showed weak inhibitory effect on the activities of CYP2B6, 2C9, 2C19, 2D6, 3A4, and compound K, while ginsenoside Rg3 showed weak inhibitory effects on CYP2B6. Other ginsenosides, Rc, Rf, Rg1, Rh1, Rf, and Re did not show significant inhibitory effects on the activities of the seven CYPs in HLM. Owing to the poor absorption of ginsenosides after oral administration in vivo, ginsenosides may not have significant side effects caused by interaction with other drugs.

• Korean Journal of Pharmacognosy
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• v.49 no.2
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• pp.85-102
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• 2018

A drug interaction is a situation in which a substance affects the activity of a drug, synergistically or antagonistically, when both are administered together. It has been shown that orally taken ginsenosides are deglycosylated by intestinal bacteria to give ginsenosides metabolites, which has been considered to be genuine pharmacological constituents and to exhibit drug interactions. Animal experimental results demonstrated that ginsenoside metabolites play an important role in the inhibitory or inductive action of both CYPs (cytochrome p450) and P-gp (p-glycoprotein), thereby can be applied as metabolic modulator to drug interactions. Very few are known on the possibility of drug interaction if taken the recommended dose of ginseng, but it has been found to act as CYPs inductor and P-gp inhibitor in any clinical trial, suggesting the risk that side effects will occur. It has been recently reported that interactions might also exist between ginseng and drugs such as warfarin, phenelzine, imatinib and raltegravir. Moreover, medicinal plants are increasingly being taken in a manner more often associated with prescription medicines. Therefore, considering the extensive applications of ginseng for safety, the aim of this review is to present a comprehensive overview of ginseng and drug interactions based upon pharmacodynamic and pharmacokinetic evidences.

• Transactions of the Korean Society of Mechanical Engineers A
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• v.34 no.11
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• pp.1595-1602
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• 2010

A disposable drug infuser is used to provide drugs to patients who are not hospitalized; in this infuser, an elastic recovery force is exerted by a diaphragm made of a rubber-like materialsuch that a constant amount of drugs is provided to a patient. The drug infuser has to control the speed and amount of drugs to be released, as well as the overall duration for which they are to be administered. However, in a drug infuser with an elastic diaphragm, the infusion pressure depends on the amount of drug remaining within the infuser, and the amount of drug infused gradually decreases as the amount remaining in the infuser decreases. In this study, a finite element procedure involving the application of the fluid-structure interaction technique was developed and the performance of the elastic type disposable drug infuser was analyzed. The optimum design for ensuring that the infusion pressure remains constant throughout the duration of usage, including during infusion and discharge, was determined by this procedure.

• The Journal of Internal Korean Medicine
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• v.29 no.4
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• pp.887-903
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• 2008

Objectives : We present some opinions to reduce the risk of herb-drug interactions through scanning "About Herbs" of the Memorial Sloan Kettering Cancer Center Website. Methods : We searched the Memorial Sloan Kettering Cancer Center Website of About Herbs and investigated herb-drug interactions. Results : There are 237 herbs and 196 drugs on About Herbs. 81.1% of herbs have fewer than 2 interactions listed.: 86.3% of drugs fewer than 3 interactions. Especially, 13 herbs were reported to have interactions with inclusive chemoagents on About Herbs. Only L-theanine has positive interaction with inclusive chemoagents. The others have negative interactions with inclusive chemoagents. 12 single chemoagents were reported to have interactions with some herbs. Especially tamoxifen-black cohosh, methotrexate-glutamin and aldesleukin-Huang Chi have positive interactions to increase the effects of the chemoagent. Conclusions : We should urgently create a risk management system of herb-drug interactions and take note of the risk of herb-drug interactions. We should build up systemic, evidence-based informations on popular herbs used by Korean cancer patients and herb-drug interactions in oncology like About Herbs.

• YAKHAK HOEJI
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• v.39 no.1
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• pp.78-84
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• 1995

Based on Computer graphics molecular modeling method, quinolone derivatives as DNA-gyrase inhibitors formed stable DNA-intercalation complex with deoxycytidilyl-3',5'-deoxy guanosine[d($C_{p}G)_{2}$] dinucleotide. When d($C_{p}G)_{2}$ and d($A_{p}T)_{2}$, were compared in order to find out which DNA could form more stable DNA-Drug complex based on interaction energy($\Delta$E) and DNA-Drug complex energy, d($C_{p}G)_{2}$ resulted in lower energy than d($A_{p}T)_{2}$.

• Bulletin of the Korean Chemical Society
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• v.35 no.8
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• pp.2317-2325
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• 2014

P-glycoprotein (P-gp) is a member of the ATP-Binding Cassette transporter superfamily and mediates transmembrane efflux of many drugs. Since it is involved in multi-drug resistance activity in various cancer cells, the development of P-gp inhibitor is one of the major concerns in anticancer therapy. Human P-gp protein has at least two "functional" drug binding sites that are called "H" site and "R" site, hence it has multi-binding-specificities. Though the amino acid residues that constitute in drug binding pockets have been proposed by previous experimental evidences, the shapes and the binding poses are not revealed clearly yet. In this study, human P-gp structure was built by homology modeling with available crystal structure of mouse P-gp as a template and docking simulations were performed with inhibitors such as verapamil, hoechst33342, and rhodamine123 to construct the interaction between human P-gp and its inhibitors. The docking simulations were performed 500 times for each inhibitor, and then the interaction frequency of the amino acids at the binding poses was analyzed. With the analysis results, we proposed highly contributing residues that constitute binding pockets of the human P-gp for the inhibitors. Using the highly contributing residues, we proposed the locations and the shapes of verapamil binding site and "R" site, and suggested the possible position of "H" site.