• Title/Summary/Keyword: drug-drug interactions

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Genetic Polymorphisms in Drug Transporters and Regulatory Xenobiotic Receptors in Korean Population

  • Lee, Sang-Seop;Shin, Jae-Gook
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2004.05a
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    • pp.27-29
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    • 2004
  • Drug transporters play an essential role in the absorption, distribution and elimination of clinical drugs, nutrients and toxicants. The importance of the transporters is exampled by therapeutic failure in cancer chemotherapy that is mainly caused by the overexpression of multidrug resistance (MDR)-related transporters. In addition, the transporters may involve in drug-drug interactions that lead to serious adverse drug responses and some transporters also contribute to inter-individual variation in drug responses. As an effort to understand the mechanism underlying the inter-individual variation of transporters activity, genetic and environmental factors influencing the expression or function of the transporters have extensively explored through last decade. Among them, genetic polymorphism of drug transporter encoding genes has generated much interest since the discovery of functional single nucleotide polymorphisms (SNP) of MDRl gene. Besides drug transporters, xenobiotic receptors also modulate drug disposition by regulating the transcription of drug metabolizing enzymes and drug transporters. Among many xenobiotic receptors, pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are two most well characterized since these receptors show wide substrate specificities and regulate the expression of various enzymes involved in drug disposition. Recently, several functional genetic polymorphisms were reported in PXR coding gene. In the present study, genetic polymorph isms of two drug transporters, MDR1 and BCRP, and two xenobiotic receptors, PXR and CAR, were investigated in Korean population.

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Practice Guideline of Use of Benzodiazepines in Psychiatric Field (정신과 영역에서 벤조다이아제핀계 약물의 사용과 문제점)

  • Oh Kang-Seob
    • Anxiety and mood
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    • v.1 no.1
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    • pp.37-42
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    • 2005
  • Benzodiazepines are widely used for a variety of conditions in psychiatric field. In this article, the author reviewed the indications, the effects on anxiety and sleep disorders, the side effects, the drug-drug interactions, and the tapering strategies. Benzodiazepines were relatively safe and useful for the treatment of anxiety and sleep disorders. However, used clinically, benzodiazepines can induce many adverse effects (e. g. over-sedation, cognitive impairments, paradoxical effects, dependence and withdrawal symptoms, and so on). Currently available informations about their effects on the developing fetus is controversial. For this reason, pregnant women and nursing mother should be cautioned against the use of benzodiazepines. Drug-drug interactions have to be considered in combination treatments. For the tapering issues, gradual tapering was important to prevent the withdrawal symptoms. Especially, the tapering schedules have to be individualized for the each long-term benzodiapzepine users.

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Cardiovascular effect of epinephrine in endodontic microsurgery: a review

  • Jang, Youngjune;Kim, Euiseong
    • Restorative Dentistry and Endodontics
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    • v.38 no.4
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    • pp.187-193
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    • 2013
  • Epinephrine is one of the most widely-used vasoconstrictors in dental treatment including endodontic microsurgery. However, the systemic safety of epinephrine has been in debate for many years because of its potential risk to cause cardiovascular complications. The purpose of this review was to assess the cardiovascular effect of epinephrine use in endodontic microsurgery. Endodontic microsurgery directly applies epinephrine into the bone cavity, and the amount is reported to be much larger than other dental surgeries. Moreover, when considering that systemic potency of intraosseous application is reported to be comparable to intravenous application, the systemic influence of epinephrine could be increased in endodontic microsurgery. Besides, pre-existing cardiovascular complications or drug interactions can enhance its systemic influence, resulting in increased susceptibility to cardiovascular complications. Although clinical studies have not reported significant complications for patients without severe systemic complications, many epinephrine-induced emergency cases are warning the cardiovascular risk related with pre-existing systemic disease or drug interactions. Epinephrine is a dose-sensitive drug, and its hypersensitivity reaction can be fatal to patients when it is related to cardiovascular complications. Therefore, clinicians should recognize the risk, and the usage of pre-operative patient evaluation, dose control and patient monitoring are required to ensure patient's safety during endodontic microsurgery.

Therapeutic Drug Monitoring (TDM) of Psychotropic Drugs (향정신성약물의 치료적 약물농도 검사)

  • Yang, Byung-Hwan
    • Korean Journal of Biological Psychiatry
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    • v.5 no.1
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    • pp.56-65
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    • 1998
  • Clinicians can use therapeutic drug monitoring(TDM) to optimise dosage decisions with psychotropic drugs, in order to maximize efficacy and prevent toxicity, especially when individuals are nonresponsive to treatment or vulnerable to adverse reactions with standard doses because age, disease states or drug interactions. Currently, therapeutic drug concentrations have been established for the TCA and lithium. There is also evidence for the usefulness of TDM with carbamazepine, valproic acid and some antipsychotic drugs. However for most psychotropic drugs this approach remains experimental. TDM-assisted psychiatric treatment is potentially useful and cost effective, particularly when applied by psychiatrists who are knowledgeable of pharmacokinetics and pharmacodynamics.

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Decreased absorption of midazolam in the stomach due to low pH induced by co-administration of Banha-sasim-tang

  • Jo, Jun Hyeon;Kim, Sun Joo;Nam, Woong Shik;Seung, Eun Ji;Lee, Sangkyu
    • Environmental Analysis Health and Toxicology
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    • v.31
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    • pp.16.1-16.9
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    • 2016
  • Objectives Banha-sasim-tang (BST), which consists of seven different herbs, is one of the most popular herbal formulae for treating gastrointestinal disorders in Eastern Asia. The commonly used herbal medicine is often co-administered with other therapeutic drugs, which raises the possibility of herb-drug interactions and may modify the clinical safety profile of therapeutic drugs. Methods We investigated the potential herb-drug interactions between BST extract and midazolam (MDZ) in mice. The area under the plasma concentration-time curve (AUC) of MDZ and 1'-hydroxymidazolam (1'-OH-MDZ) was evaluated for both oral and intraperitoneal administration of MDZ, following oral administration of BST (0.5 and 1 g/kg). Results It was found that the AUC of MDZ and 1'-OH-MDZ was lower in case of oral administration of MDZ. Administration of BST extract was not associated with hepatic cytochrome P450 activity. BST extract induced a strong reduction in pH and it has been reported that oral mucosal absorption of MDZ is lower at low pH. The decreased absorption rate of MDZ might be caused by the ingredients of BST and may not be related to other factors such as increased excretion of MDZ by P-glycoprotein. Conclusions The altered pharmacokinetics of midazolam caused by co-administration with BST in vivo could be attributed to a decrease in pH and subsequent reduction of MDZ absorption rate.

Invertebrate Models Used for Characterization of Drug Dependence and Development of Anti-Drug Dependent Agents

  • Chang Hyun-Sook;Kim Ha-Won;Lee Dong-Hee
    • Biomolecules & Therapeutics
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    • v.14 no.1
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    • pp.1-10
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    • 2006
  • Drug dependence deals a heavy socioeconomic burden to the society. For adolescents, the damage from drug dependence is greater than adults considering their higher susceptibility to drug effect and increasing chance for violence leading to criminal punishment process. Habitual drug use depends on genetic and environmental factors and the complex interactions between the two. Mammalian model systems have been useful in understanding the neurochemical and cellular impacts of abused drugs on specific regions of the brain, and in identifying the molecular targets of drugs. More elucidation is required whether biological effects of drugs actually cause the habitual dependence at the cellular level. Although there is much insight available on the nature of drug abuse problems, none of the systems designed to help drug dependent individuals is efficient in screening functional ingredients of the drug, and thus resulting in the failure of helping drug dependent individuals recover from drug dependence. Alternative model systems draw the attention of researchers, such as the invertebrate model systems of nematodes (Caenorhabditis elegans) and fruit flies (Drosophila melanogaster). These models should provide new insight into the mechanisms leading to the behavior of drug users (even functional studies analyzing molecular mechanism), and screening useful components to help remove drug dependence among drug users. The relatively simple anatomy and gene expression of the invertebrate model systems should enable researchers to coordinate current knowledge on drug abuse. Furthermore, the invertebrate model systems should facilitate advance in experiments on the susceptibility of specific genetic backgrounds and the interaction between genetic factors to drug dependence.

Nanocellulose Applications for Drug Delivery: A Review

  • Lee, Seung-Hwan;Kim, Hyun-Ji;Kim, Jin-Chul
    • Journal of Forest and Environmental Science
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    • v.35 no.3
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    • pp.141-149
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    • 2019
  • Nanocellulose, which can exist as either cellulose nanocrystals or cellulose nanofibrils, has been used as a biomaterial for drug delivery owing to its non-immunogenicity, biocompatibility, high specific area, good mechanical properties, and variability for chemical modification. Various water-soluble drugs can be bound to and released from nanocelluloses through electrostatic interactions. The high specific surface area of nanocellulose allows for high specific drug loading. Additionally, a broad spectrum of drugs can bind to nanocellulose after facile chemical modifications of its surface. Controlled release can be achieved for various pharmaceuticals when the nanocellulose surface is chemically modified or physically formulated in an adequate manner. This review summarizes the potential applications of nanocelluloses in drug delivery according to published studies on drug delivery systems.

Gliclazide compatibility with some common chemically reactive excipients; using different analytical techniques

  • Jabbari, Hamideh Najjarpour;Shabani, Mohammad;Monajjemzadeh, Farnaz
    • Analytical Science and Technology
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    • v.34 no.2
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    • pp.46-55
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    • 2021
  • Evaluation of drug-excipient compatibility is one of the basic steps in the preformulation of pharmaceutical dosage forms. Some reactive excipients have been known so far which may cause stability problems for drug molecules in pharmaceutical dosage forms. The aim of this study was to evaluate drugexcipient compatibility of gliclazide with some common pharmaceutical excipients, known for their ability to incorporate in drug-excipient interactions. Binary mixtures were prepared using lactose, magnesium stearate, polyvinylpyrrolidone, sodium starch glycolate, polyethylene glycol 2000 and dicalcium phosphate. Based on the results; gliclazide was incompatible with all tested excipients; but not with dicalcium phosphate. DSC (Differential Scanning Calorimetry) results were in accordance with HPLC (High Pressure liquid chromatography) data and were more predictive than FTIR (Fourier Transform Infrared Spectroscopy). Drug and reactive excipients incompatibility was fully discussed and documented. It is advisable to avoid incompatible excipients or carefully monitor the drug stability when incorporating such excipients in final formulation designs.

Potential Drug Interactions in Cancer Patients on Oral Kinase Inhibitors (경구용 활성효소 억제제 복용 암환자의 잠재적 약물상호작용 연구)

  • Jung, Eun-Hee;Bang, Joon Seok;Lee, Yu Jeung
    • 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.

Pharmacokinetic Studies and Drug-drug Interactions of Herbal Medicine (생약제제의 약물동태 연구 및 상호작용)

  • Jung, Won-Pill;Noh, Keum-Han;Lim, Mi-Sun;Lee, Hae-Won;Kim, Eun-Jung;Yoon, Young-Ran;Kang, Won-Ku
    • Korean Journal of Clinical Pharmacy
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    • v.20 no.2
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    • pp.99-106
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    • 2010
  • Drugs mostly represent an efficacy or an adverse effect according to their dosage and/or plasma concentrations. Therefore, to investigate the pharmacokinetic behavior of drugs including herbal medicines is necessary both to maximize the drug action and to minimize the adverse effect. To date, pharmacokinetic studies of herbal medicines have been conducted by some experts in this field on the bases of science and knowledge in Korea. On the other hand, in advanced countries, a typical series of pharmacokinetic studies has been conducted by using a harmonized guidance established. Consequently, an administrative support on these studies has to be needed in Korea as well. This study aimed to establish a draft guidance on pharmacokinetic studies of herbal medicines in non-clinical and clinical studies. Literatures previously published as well as guidances in the US, Europe and Japan were summarized for the present guidance. Effect of herbal medicines was listed on the proteins in charge of drug metabolism and transportation, as well as on the pharmacokinetics of chemical drugs. The present suggestion might be helpful to proceed pharmacokinetic studies of herbal medicines efficiently, and further polish should be needed in terms of an administrative point of view.