• Journal of Photoscience
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• v.12 no.1
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• pp.25-32
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• 2005

Binding of N-Alkyl phenothiazines (NAP) to bovine serum albumin (BSA) was studied by spectroscopic methods.It was found that the phenothiazine ring common to all drugs makes major contribution to interaction. However, the nature of alkylamino group at position 10 influences the protein binding significantly. Stern-Volmer plots indicated the presence of static component in the quenching mechanism. The high magnitude of rate constant of quenching indicated that the process of energy transfer occurs by intermolecular interaction and thus the drug-binding site is in close proximity to tryptophan residues of BSA. Binding studies in presence of hydrophobic probe, 8-anilino-1-naphthalein-sulphonic acid showed that there is hydrophobic interaction between drug and the probe and they do not share common sites in BSA. Thermodynamic parameters obtained from data at different temperatures showed that the binding of NAP to BSA predominantly involve hydrophobic forces. The effects of some cations and anions common ions were investigated on NAP-BSA interactions. The CD spectrum of BSA in presence of drug showedthat binding of drug leads to change in the helicity of the protein.

• Korean Journal of Clinical Pharmacy
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• v.23 no.2
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• pp.129-136
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• 2013

Objectives: Among many new drugs that are under investigation with intent to treat cancer, oral kinase inhibitors are proven to be effective in numerous clinical trials and easy to administer. Due to these advantages the use of oral kinase inhibitors is increasing. Oral kinase inhibitors are metabolized by CYP450 which can result either increase of adverse effect or decrease of drug effect by drug interaction when used concurrently with other agents. In this research, the medication records of patients on oral kinase inhibitors from Oct. 2010 to Nov. 2011 were reviewed to investigate potential drug interactions. Methods: From Oct. 2010 to Nov. 2011, cancer patients in Inha University Hospital who took oral kinase inhibitors more than once were included. The patients' medication records were reviewed to list out concurrent medications that have interaction potential with oral kinase inhibitors, the frequency of concurrent use, and the severity of interaction result using Micromedex$^{(R)}$ and Lexicomp-online$^{(R)}$ as references. Results: As a result, 90 cases of drug with interaction potential were prescribed by Micromedex$^{(R)}$ and 179 cases by Lexicomp-online$^{(R)}$ data. In case of severity, 33.3% by Micromedex$^{(R)}$ and 26.3% by Lexicomp-online$^{(R)}$ were categorized as Major and 65.6% by Micromedex$^{(R)}$ and 72.6% by Lexicomp-online$^{(R)}$ as Moderate. The number of adverse events was 92 cases which 58.7% were on skin and 19.6% on Gastro-intestinal tract. Conclusions: Considerable number of drug with interaction potential was used though each oral kinase inhibitors showed differences in extent. Hence there exists the risk of drug interaction in patients taking oral kinase inhibitors with other drugs.

• Health Policy and Management
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• v.7 no.2
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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.

• Journal of Preventive Medicine and Public Health
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• v.35 no.1
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• pp.41-48
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• 2002

Objectives : To review the drug prescription pattern of antiulcerative agents for elderly inpatients, Methods : The study population comprised inpatients of community hospitals who were members of the Korean Elderly Pharmacoepidemiologic Cohort (KEPEC), aged 65 years or over, beneficiaries of the Korea Medical Insurance Corporation (KMIC) and residing in Busan city in 1993. The drug prescription information was collected from the claims data of hospitals where the cohort members received medical care between January 1993 and December 1594. The information included personal identification, age, gender, diagnosis, drug dosage, date of hospital admission and name of medical institutions where the study subjects received drug prescriptions. The data analysis produced outcomes in terms of distribution of antiulcerative agents by class and by medical institution and trend of relative prescription, Analysis was also performed in terms of combined prescriptions of antiulceratives and drugs that could induce risk from drug interaction with antiulceratives. Results : The number of patients prescribed antiulcerative agents was 1,059 (64,9%) male and 1,724 (65.5%) female among the total inpatients. An antacid and composite agent was the most frequently prescribed antiulcerative agent (70.8%), followed by $H_2$ antagonist (16.0%), Among the potential drugs that could induce risk from drug interaction with the antiulcerative agents, diazepam was the most frequently prescribed. The proportion of diazepam co-prescription was 22.5% of the total cimetidine prescriptions and 14.5% of the fetal omeprazole prescriptions. Conclusions : Antiulcerative drugs were frequently prescribed in the elderly inpatients. The adverse drug reaction could possibly be due to drug interaction. The study results could be used as fundamental data for further drug utilization review of antiulceratiye agents.

• Toxicological Research
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• v.23 no.1
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• pp.1-9
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• 2007

Transporters are membrane proteins that mediate the transfer of substrate across the cellular membrane. In this overview, the characteristics and the toxicological relevance were discussed for various types of transporters. For drug transporters, the overview focused on ATP-binding cassette transporters and solute carrier family 21A/22A member transporters. Except for OCTN transporters and OATP transporters, drug transporters tend to have broad substrate specificity, suggesting drug-drug interaction at the level of transport processes (e.g., interaction between methotrexate and non-steroidal anti-inflammatory agents) is likely. For metal transporters, transporters for zinc, copper and multiple metals were discussed in this overview. These metal transporters have comparatively narrow substrate specificity, except for multiple metal transporters, suggesting that inter-substrate interaction at the level of transport is less likely. In contrast, the expressions of the transporters are often regulated by their substrates, suggesting cellular adaptation mechanism exists for these transporters. The drug-drug interactions in drug transporters and the cellular adaptation mechanisms for metal transporters are likely to lead to alterations in pharmacokinetics and cellular metal homeostasis, which may be linked to the development of toxicity. Therefore, the transporter-mediated alterations may have toxicological relevance.

• Toxicological Research
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• v.31 no.2
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• pp.137-149
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• 2015

Human hepatocytes, with complete hepatic metabolizing enzymes, transporters and cofactors, represent the gold standard for in vitro evaluation of drug metabolism, drug-drug interactions, and hepatotoxicity. Successful cryopreservation of human hepatocytes enables this experimental system to be used routinely. The use of human hepatocytes to evaluate two major adverse drug properties: drug-drug interactions and hepatotoxicity, are summarized in this review. The application of human hepatocytes in metabolism-based drug-drug interaction includes metabolite profiling, pathway identification, P450 inhibition, P450 induction, and uptake and efflux transporter inhibition. The application of human hepatocytes in toxicity evaluation includes in vitro hepatotoxicity and metabolism-based drug toxicity determination. A novel system, the Integrated Discrete Multiple Organ Co-culture (IdMOC) which allows the evaluation of nonhepatic toxicity in the presence of hepatic metabolism, is described.

• Biomolecules & Therapeutics
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• v.30 no.1
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• pp.1-18
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• 2022

Drug-drug interactions are a major cause of hospitalization and deaths related to drug use. A large fraction of these is due to inhibition of enzymes involved in drug metabolism and transport, particularly cytochrome P450 (P450) enzymes. Understanding basic mechanisms of enzyme inhibition is important, particularly in terms of reversibility and the use of the appropriate parameters. In addition to drug-drug interactions, issues have involved interactions of drugs with foods and natural products related to P450 enzymes. Predicting drug-drug interactions is a major effort in drug development in the pharmaceutical industry and regulatory agencies. With appropriate in vitro experiments, it is possible to stratify clinical drug-drug interaction studies. A better understanding of drug interactions and training of physicians and pharmacists has developed. Finally, some P450s have been the targets of drugs in some cancers and other disease states.

• Journal of Pharmaceutical Investigation
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• v.26 no.2
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• pp.119-124
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• 1996

To develop oral controlled release dosage forms, ionic interactions between polymers and drugs were evaluated. Hydroxypropylmethyl cellulose and carboxymethylene were used as model nonionic and ionic polymers, respectively. 5-fluorouracil, propranolol-HCl and sodium salicylate were selected as model nonionic, cationic and anionic, respectively. Polymer-drug mixtures were compressed into tablets and drug release kinetics from these tablets were determined. Drug release from the tablets made of the nonionic polymer was not affected by the charge of drugs, rather, was regulated by the solubility of drugs in different pH releasing media. However, drug release kinetics were significantly affected when drug-polymer ionic interactions exist. Enhanced drug release was observed from anionic drug-anionic polymer tablets due to ionic repulsion, whereas drug release was retarded in cationic drug-anionic polymer tablets owing to ionic attractive force. Therefore, the results suggested that the polymer-drug interactions are important factors in designing controlled release dosage forms.

• Toxicological Research
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• v.33 no.1
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• pp.25-30
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• 2017

Saccharin, the first artificial sweetener, was discovered in 1879 that do not have any calories and is approximately 200~700 times sweeter than sugar. Saccharin was the most common domestically produced sweetener in Korea in 2010, and it has been used as an alternative to sugar in many products. The interaction between artificial sweeteners and drugs may affect the drug metabolism in patients with diabetes, cancer, and liver damage, this interaction has not been clarified thus far. Here, we examined the effects of the potential saccharin-drug interaction on the activities of 5 cytochrome P450 (CYPs) in male ICR mice; further, we examined the effects of saccharin (4,000 mg/kg) on the pharmacokinetics of bupropion after pretreatment of mice with saccharin for 7 days and after concomitant administration of bupropion and saccharin. Our results showed saccharin did not have a significant effect on the 5 CYPs in the S9 fractions obtained from the liver of mice. In addition, we observed no differences in the pharmacokinetic parameters of bupropion between the control group and the groups pretreated with saccharin and that receiving concomitant administration of saccharin. Thus, our results showed that saccharin is safe and the risk of saccharin-drug interaction is very low.

• Bulletin of the Korean Chemical Society
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• v.27 no.9
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• pp.1285-1286
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• 2006