• Title/Summary/Keyword: drug-interaction

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Merging the old with the new: a cybermedicine marriage for oncology interactions with traditional herbal therapies and complementary medicines

  • Yap, Kevin Yi-Lwern;Lim, Ken Juin
    • CELLMED
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    • v.2 no.2
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    • pp.18.1-18.16
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    • 2012
  • An oncology-specific database called OncoRx (http://bit.ly/cancerRx) was previously set up in cyberspace to aid clinicians in identifying interactions of anticancer drugs (ACDs) and chemotherapy regimens with traditional Chinese medicines (TCMs) and complementary and alternative medicines (CAMs). Since then, users have requested the drug-CAM interactions (DCIs) of 5 specific CAMs (cranberry, melatonin, co-enzyme Q10, huachansu, reishi mushroom) to be updated in the database. Pharmacokinetic properties (metabolism, enzyme induction/inhibition, elimination), TCM properties and DCIs of each CAM were collated with 117 ACDs using 9 hardcopy compendia and online databases as resources. Additionally, individual ACDs and CAMs were used as keywords for PubMed searches in combination with the terms 'anticancer drugs', 'drug interactions', 'herb-drug/drug-herb interactions', 'pharmacokinetic interactions' and 'pharmacodynamic interactions'. DCI parameters consisted of interaction effects, evidence summaries, proposed management plans and alternative non-interacting CAMs, together with relevant citations and update dates of the DCIs. OncoRx is also used as a case to introduce the "Four Pharmaco-cybernetic Maxims" of quality, quantity, relationship and manner to developers of digital healthcare tools. Its role in Hayne's "5S" hierarchy of research evidence is also presented. OncoRx is meant to complement existing DCI resources for clinicians and alternative medicine practitioners as an additional drug information resource that provides evidence-based DCI information for ACD-CAM interactions.

Complexation of Piroxicam and Tenoxicam with $Hydroxypropyl-{\beta}-cyclodextrin$ (히드록시프로필-베타-시클로덱스트린과 피록시캄 및 테녹시캄 간의 복합체 형성)

  • Kim, Ju-Hyun;Choi, Hoo-Kyun
    • Journal of Pharmaceutical Investigation
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    • v.30 no.1
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    • pp.33-37
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    • 2000
  • One of the methods to increase the solubility of a drug is to use complexation with a cyclodextrin. Due to the hydrophobic nature of the interior cavity of the cyclodextrin, it has been known that undissociated lipophilic drugs can be included within the cyclodextrin by hydrophobic interaction. Recently, inclusion of hydrophilic or dissociated form of a drug has been investigated. In this study, the synergism of pH and complexation with $hydroxypropy-{\beta}-cyclodextrin\;(HP\;{\beta}\;CD)$ to increase the solubility of two oxicam derivatives was investigated. In addition, the effect of partition coefficient of dissociated and undissociated form of the drug on the extent of complexation with HP ${\beta}$ CD was studied. The solubility was measured by equilibrium solubility method. The solubility of tenoxicam and piroxicam increased exponentially with an increase in solution pH above the pKa of the drug in the presence and absence of HP ${\beta}$ CD. The solubility of the drugs increased linearly as a function of HP ${\beta}CD$ concentration at fixed pH. Although the stability constant of ionized species is less than that of the unionized species, the concentration of the ionized drug complex is greater than that of the unionized drug complex due to higher concentration of ionized species at pH 7.3.

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Antibacterial and Pharmacological Evaluation of Fluoroquinolones: A Chemoinformatics Approach

  • Sood, Damini;Kumar, Neeraj;Singh, Aarushi;Sakharkar, Meena Kishore;Tomar, Vartika;Chandra, Ramesh
    • Genomics & Informatics
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    • v.16 no.3
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    • pp.44-51
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    • 2018
  • Fluoroquinolone (FQ) antibiotics are an important class of synthetic antibacterial agents. These are the most extensively used drugs for treating bacterial infections in the field of both human and veterinary medicine. Herein, the antibacterial and pharmacological properties of four fluoroquinolones: lomefloxacin, norfloxacin, ciprofloxacin, and ofloxacin have been studied. The objective of this study was to analyze the antibacterial characteristics of the different fluoroquinolones. Also, the pharmacological properties of the compounds including the Lipinski rule of five, absorption, distribution, metabolism, and excretion, LD50, drug likeliness, and toxicity were evaluated. We found that among all four FQ molecules, ofloxacin showed the highest antibacterial activity through in silico assays with a strong interaction (-38.52 kJ/mol) with the antibacterial target protein (topoisomerase-II DNA gyrase enzyme). The pharmacological and pharmacokinetic analysis also showed that the compounds ciprofloxacin, ofloxacin, lomefloxacin and norfloxacin have good pharmacological properties. Notably, ofloxacin was found to possess an IGC50 (concentration needed to inhibit 50% growth) value of $0.286{\mu}g/L$ against the Tetrahymena pyriformis protozoa. It also tested negative for the Ames toxicity test, showing its non-carcinogenic character.

Relationships among Depression, Self-rated Health, Health Behaviors and Drug Abuse by Job Status (근로여부에 따른 약물오남용과 우울, 주관적 건강상태, 건강행태와의 관련성)

  • Chae, Su Mi;Jeong, Jin Wook;Lee, Sang Young;Heo, Kyung Hwa
    • Korean Journal of Occupational Health Nursing
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    • v.24 no.3
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    • pp.245-257
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    • 2015
  • Purpose: This study was performed to investigate the present condition of drug abuse and its association with depression, self-rated health and health behaviors by job status in Korean adults. Methods: Data were derived from the study on four addiction problem and suicide in 2014. Multiple logistic regression was used to analyze patterns of drug abuse according to depression, self-rated health and health behaviors. Results: The prevalence of drug abuse during the past year was 17.1% of the 4,018 subjects. About 3.3 times risk for drug abuse was found among individuals who had high depression scores. The risk of drug abuse was higher among those who were smoking (OR:1.46, 95% CI:1.17~1.83), drinking more frequently (OR:1.30, 95% CI:1.07~1.58), sleeping insufficiently (OR:1.31, 95% CI:1.03~1.67), eating irregularly (OR:1.45, 95% CI:1.19~1.76). Drug abuse problem was detected more seriously among employed than unemployed adults. Conclusion: Health-related behaviors, such as smoking, drinking, sleeping, eating should be considered simultaneously when designing strategies to deal with drug abuse problem, and it is important to understand the interaction between drug abuse and mental health. Furthermore, workplace based intervention can be effective in solving drug abuse problem.

Drug Interaction of Nalidixic Acid and Probenecid in Rabbits (Nalidixic Acid와 Probenecid의 약물 상호 작용)

  • 최준식
    • YAKHAK HOEJI
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    • v.27 no.2
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    • pp.133-138
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    • 1983
  • The interaction between nalidixic acid and probenecid was studied pharmacokinetically in rabbits. The blood level and the area under the concentration curve(AUC) of nalidixic acid administered orally in dose of 100mg/kg was elevated by the coadministration of probenecid. Probenecid inhibited both the urinary excretion and the biliary excretion of nalidixic acid. Therefore, biological half-life of nalidixic acid was prolonged by the coadministrarion of probenecid. It was considered that the coadmini-stration of probenecid is more desirable than the single administration of nalidixic acid for the therapeutic effect.

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A Study on the Status of Health and Medication in the Elderly (노인의 건강상태와 복약실태)

  • Cho Won Sun
    • Journal of Korean Public Health Nursing
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    • v.14 no.2
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    • pp.431-445
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    • 2000
  • In general the prevalence of old people is high and frequently have multiple diseases and symtoms requiring treatment. The nature of illness in the elderly has to be faced, and drugs do have an important part in the treatment of that illness. The purpose of this study were to describe health status and medication, and to provide some basic data for elderly's health education, especially for the right medication. Body mass index, self perceived health status, activities of daily living, disease and experience of past operation were surveyed to recognize the 249 elderly's actual health status. The degree of the elderly's understanding the way of medication, experience of side effects, experience of drug combination and incidence of drug adverse reaction along with drug combination were examined for medication. The aged $women(BMI; 10.7\pm13.3\%)$ overweighed the aged $men(BMI; 4.0\pm10.4\%)$. $69.0\%$ of them recognized their health good. Their activities of daily living were diminished following by the age group(p=0.0068) and relationship with self perceived health status were very significant(p=0.0005). They(192 elderly) suffered from multiple disease such as $osteoarthritis(49.5\%)$, $hypertension(32.0\%)$, gastric $disorder(16.1%)$, $diabetes(14.6\%)$, $osteomalacia(10.9\%)$, cardiovascular $disease(9.9\%)$, senile $cataract(5.7\%)$, skin $rash(5.2\%)$, liver $disease(4.2\%)$, kidney $disease(3.6\%)$, spinal cord $problem(3.6\%)$, respiratory $disease(2.1\%)$ $tuberculosis(1.0\%)\;etc(1.0\%).$ $28.3\%$ of them replied that they had an operation for appendictis senile cataract, peptic ulcer, spinal cord problem, pleurisy, hemorrhoid and the rest. Most of $them(87.4\%)$ knew the way very well how to use drugs, and $21.6\%$ of the replied 171 elderly experienced adverse drug reaction. Drug compliance rate were $high(83.6\%)$. In our study 56.9% of the 167 elderly took several medicine together. And $18.9\%$ of the 95 elderly who did drug combination had an experience of drug interaction. One person kept average 5.5 kinds of drugs at home among 243 elderly. They kept $digestives(79.4\%)$, $ointments(68.7\%)$, $vitamins(59.7\%)$, $analgesics(59.7\%)$, cold $medicines(45.3\%)$ antiarthritic $drugs(33.3\%)$, health $foods(27.7\%)$, antihypertensive $drugs(25.1\%)$, anti peptic ulcer $drugs(24.7\%)$, $laxatives(19.8\%)$, $antacids(16.5\%),\;antibiotics(l6.5\%)$, hypoglycemic $agents(10.3\%)$, cardiac $stimulants(7.0\%)$, $diuretics(4.5\%)$, antiarrhythmic $drugs(4.9\%)$, anti anginal $drugs(4.1\%)$, $hypnotics(3.3\%)$, $etc(38.3\%)$. With this result, we ascertain that polypharmacy in the elderly caused by multiple disease is common, which lead to drug interaction. So our task is to educate elderly how to use drugs in order to maximize their efficiency and to minimize their adverse effects.

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Bioequivalence Approaches for Highly Variable Drugs: Issue and Solution (개체 변이가 큰 약물 (highly variable drug)의 생물학적동등성 시험을 위한 실험설계 및 평가방법)

  • Baek, In-Hwan;Seong, Soo-Hyeon;Kwon, Kwang-Il
    • Korean Journal of Clinical Pharmacy
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    • v.19 no.1
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    • pp.50-60
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    • 2009
  • Highly variable drugs (within-subject variability greater than 30%) have been difficult to meet current regulatory acceptance criteria using a reasonable number of study subjects. In this study, we reviewed previous studies presenting alternative approaches for bioequivalence evaluation of highly variable drugs, and focused on an approach for widening the bioequivalence acceptance limits using within-subject variability. We discussed the suggested five solutions for highly variable drug including the deletion of $C_{max}$ of the bioequivalence criteria, direct expansion of bioequivalence limit, multiple dose studies in steady state, bioequivalence assessment on the metabolite, add-on study, and widening the bioequivalence acceptance limits based on reference variability. The methods for widening of bioequivalence limits based on reference variability are scaled average bioequivalence containing within-subject variability on reference drug (${\sigma}_{WR}$), population bioequivalence derived from total variability on reference drug (${\sigma}_{TR}$) and test drug (${\sigma}_{TT}$), and individual bioequivalence derived from subject by formulation interaction variability (${\sigma}_D$) and within subject variability on reference drug (${\sigma}_{WR}$) and test drug (${\sigma}_{TR}$). To apply these methods, the switching variability (${\sigma}_0$) will have to be set by the regulatory authorities. The proposals of bioequivalence evaluation approach for the highly variable in Korea are presented for both of new drug and reevaluation drug.

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Bosentan and Rifampin Interactions Modulate Influx Transporter and Cytochrome P450 Expression and Activities in Primary Human Hepatocytes

  • Han, Kyoung-Moon;Ahn, Sun-Young;Seo, Hyewon;Yun, Jaesuk;Cha, Hye Jin;Shin, Ji-Soon;Kim, Young-Hoon;Kim, Hyungsoo;Park, Hye-kyung;Lee, Yong-Moon
    • 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.

A Bayesian Poisson model for analyzing adverse drug reaction in self-controlled case series studies (베이지안 포아송 모형을 적용한 자기-대조 환자군 연구에서의 약물상호작용 위험도 분석)

  • Lee, Eunchae;Hwang, Beom Seuk
    • The Korean Journal of Applied Statistics
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    • v.33 no.2
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    • pp.203-213
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    • 2020
  • The self-controlled case series (SCCS) study measures the relative risk of exposure to exposure period by setting the non-exposure period of the patient as the control period without a separate control group. This method minimizes the bias that occurs when selecting a control group and is often used to measure the risk of adverse events after taking a drug. This study used SCCS to examine the increased risk of side effects when two or more drugs are used in combination. A conditional Poisson model is assumed and analyzed for drug interaction between the narcotic analgesic, tramadol and multi-frequency combination drugs. Bayesian inference is used to solve the overfitting problem of MLE and the normal or Laplace prior distributions are used to measure the sensitivity of the prior distribution.

Current Status of Herb-Drug Interaction Information and Information Database in Korea (국내 한약-양약 상호작용 연구논문 분석을 통한 상호작용 정보 현황파악 및 제공방안에 대한 연구)

  • Park, Soo-Jin;Kwon, Young-Kyu;Shin, Jae-Gook
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.24 no.4
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    • pp.543-552
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    • 2010
  • The objectives of this study are to examine the current status and problems of herb-drug interaction (HDI) information and information database in Korea and suggest the better way to establish useful HDI database. We collected HDI studies that published in Korea and analyzed according to objective, methods, selection criteria of herbs, number of study, correlation between study subject and frequently used herbal medicine (HM). Then we selected representative HM database on the internet made by Korea Food and Drug Administration (KFDA) among the several databases and analyzed its contents related to HDI. Several HDI studies were carried out from laboratory based research to clinical trials and HM databases have been developed for providing information about different aspects of traditional Korean medicine. But the information of HDI and information database are still far from practical applications because there are no coherence to select study subjects and methods among researchers. So, it is necessary to build up HDI database led by the government for providing systematic HDI information. HDI information database is expected to be able to provide useful evidence for health professionals in prescription and consultation to reduce the chance of adverse effects and improve the quality of medical care.