• Biomolecules & Therapeutics
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• 제19권1호
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• pp.1-8
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• 2011

G-protein coupled receptors (GPCRs) constitute an important class of drug targets and are involved in every aspect of human physiology including sleep regulation, blood pressure, mood, food intake, perception of pain, control of cancer growth, and immune response. Radiometric assays have been the classic method used during the search for potential therapeutics acting at various GPCRs for most GPCR-based drug discovery research programs. An increasing number of diverse small molecules, together with novel GPCR targets identified from genomics efforts, necessitates the use of high-throughput assays with a good sensitivity and specificity. Currently, a wide array of high-throughput tools for research on GPCRs is available and can be used to study receptor-ligand interaction, receptor driven functional response, receptor-receptor interaction,and receptor internalization. Many of the assay technologies are based on luminescence or fluorescence and can be easily applied in cell based models to reduce gaps between in vitro and in vivo studies for drug discovery processes. Especially, cell based models for GPCR can be efficiently employed to deconvolute the integrated information concerning the ligand-receptor-function axis obtained from label-free detection technology. This review covers various platform technologies used for the research of GPCRs, concentrating on the principal, non-radiometric homogeneous assay technologies. As current technology is rapidly advancing, the combination of probe chemistry, optical instruments, and GPCR biology will provide us with many new technologies to apply in the future.

• Journal of Photoscience
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• 제11권1호
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• pp.29-33
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• 2004

The mechanism of interaction of cyanocobalamin (CB) with bovine serum albumin (BSA) has been investigated by spectrofluorometric and circular dichroism methods. Association constant for the CB-BSA system showed that the interaction is non-covalent in nature. Binding studies in the presence of an hydrophobic probe, 8-anilino-l-naphthalene sulphonic acid, sodium salt (ANS) showed that there is hydrophobic interaction between CB and ANS and they do not share common sites in BSA. Stern-Volmer analysis of fluorescence quenching data showed that the fraction of fluorophore (protein) accessible to the quencher (CB) was close to unity indicating thereby that both tryptophan residues of BSA are involved in drug-protein interaction. The rate constant for quenching, greater than $10^{10}$ $M^{-1}$ $s^{-1}$, indicated that the drug binding site is in close proximity to tryptophan residue of BSA. Thermodynamic parameters obtained from data at different temperatures showed that the binding of CB to BSA involves hydrophobic bonds predominantly. Significant increase in concentration of free drug was observed for CB in presence of paracetamol. Circular dichroism studies revealed the change in helicity of BSA due to binding of CB to BSA.

• Archives of Pharmacal Research
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• 제14권4호
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• pp.336-341
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• 1991

The effect of bovine serum albumin (BSA) on the encapsulation efficiency and stability of liposomes containing methotrexate (MTX) having different surface charges and cholesterol contents were investigated. The encapsulation efficiency of MTX was lower and the release of MTX was faster by the addition of BSA. The leaking of MTX from lipid bilayer depends upon the BSA concentrations. These results may be derived from the interaction of BSA with lipid bilayers. The dynamic structural changes of BSA were monitored indirectly using circular dichroism spectra. Observed dynamic structural changes of BSA with liposomes are presumed to reflect the interaction of BSA with liposomes. Negatively charged liposomes have more strong interaction with BSA than neutral and positively charged liposomes. BSA attacks lipid bilayers whether it is at the inner or at the outer phase of lipid bilayer and induces leakage of entrapped MTX. Especially, negatively charged liposomes are more sensitive than others. The inclusion of cholesterol in the lipid layers inhibits the interaction of BSA with liposomes and shows protective effect against BSA-induced leakage of MTX. To endure the attacking of BSA liposomes as drug carriers should be made using cholesterol.

• Mass Spectrometry Letters
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• 제7권4호
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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.

• 생약학회지
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• 제49권2호
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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.

• 대한기계학회논문집A
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• 제34권11호
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• pp.1595-1602
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• 2010

본 논문은 유체-구조 상호작용기법을 활용하여 약물을 일정하게 공급할 수 있는 약물주입기의 성능을 예측하고 이를 바탕으로 탄성체 구조의 최적 설계안을 제안한다. 탄성체 약물주입기는 지속적인 약물치료를 필요로 하는 재택환자에게 일정하고 안정된 속도로 약물을 주입하기 위해 개발되었으며, 약물을 수용하는 탄성체의 회복력을 이용하여 일정시간 동안 지속적으로 약물을 공급하는 장치이다. 기존의 탄성체 약물주입펌프는 약물의 잔여량에 따라 주입 압력이 변하고, 약물의 주입량이 시간이 지남에 따라 감소하는 문제점이 있다. 이를 해결하기 위하여 약물이 주입되고 배출되는 전 단계에 걸쳐 일정한 압력을 유지하도록 기구부를 최적설계하고, 유한요소해석 및 실험을 통해 성능을 검증하였다.

• 보건행정학회지
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• 제7권2호
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• pp.89-108
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• 1997

The purpose of this study is to investigate drug information sources which influence physician's prescriptions, and to compare the differences of drugh information sources between private practitioners and hospital physicians. In addition, the ultimate goal of this study is to provide better quality of drug information for both groups of physicians through the professional drug information system. 264 physicians, including general practitioners and all types of specialists who were working in hospitals and private clinics in Taejon and Chungnam area, participated in this study which was conducted by mail. The results are summarized as follows ; 1. Both physician groups received drug informations mainly from medical journals, but there were differences in secondary sources of drug information. Namely, hospital physicians got drug information from annual meetings and textbooks, and private practitioners got it from detail men and colleagues. 2. Drug effect was the first consideration for drug selection in both physician groups. But, in the 2nd consideration, private practitioners concerned about the price, insurance and rebates, but hospital physicians were not. 3. Only 9.2% of the private practitioners satisfied with the sufficiency of drug information, whereas 22.0% of hospital physicians satisfied with it. The most insufficient area of information was drug interaction in both groups and 91.9% of the physicians suggested that a professional drug information system should be introduced. 4. Both physician groups had contacted with detail men frequently. However, it was rare for them to contact with a pharmacist. This phenomenon was more severe in the case of private practitioners. 5. Neither physician groups knew very much about drug informatio centers. However, they would be willig to participate if a professional drug information system were established. Also, they indicated that the information most required was drug interaction.

• 약학회지
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• 제31권4호
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• pp.204-212
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• 1987

Rifampicin is an indispensable drug along with isoniazid for the control of tuberculosis and is usually prescribed as the combination of rifampicin and isoniazid. This paper is attemtped to investigate the interaction of rifampicin and isoniazid. Isoniazid was administered orally at a dose of 30mg/kg of rabbits pretreated with rifampicin 7.5mg/kg, 15mg/kg, and 30mg/kg, respectively twice daily for 9 days. The results are as follows: The blood level and relative bioavailability of isoniazid were decreased significantly (p<0.05) by rifampicin at a dose of 15mg/kg and 30mg/kg. The renal clearance of total isoniazid and ratio of its metabolites to isoniazid were increased significantly (p<0.05) by rifampicin at a dose of 15mg/kg and 30mg/kg. It seemed to be due to enzyme induction by rifampicin. Elimination rate constant ($\beta$) of isoniazid was increased and half life ($t_{1/2$\beta}$) was decreased by rifampicin pretreatment. Dosage regimen of isoniazid after long term administration of rifampicin should be adjusted carefully.

• Journal of Pharmaceutical Investigation
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• 제23권1호
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• pp.27-32
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• 1993

Pharmacokinetic drug interaction between phenytoin and diltiazem was investigated following i.v. administration concomitantly to rabbits. Diltiazem was coadministered at doses of 1, 2 and 3 mg/kg, respectively, with phenytoin (5 mg/kg) to rabbits. 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 2 mg and 3 mg/kg of diltiazem. From the results of this experiment, it is desirable that dosage regimen of phenytoin should be adjusted and that therapeutic drug monitoring should be practiced for reduction of side or toxic effect when phenytoin should be administered with diltiazem in clinical practice.

• 대한한방내과학회지
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• 제29권4호
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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.