• Title/Summary/Keyword: Drug-drug interaction

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Characterization of Sterically Stabilized Liposomes and Their Stability in Rat Plasma in Vitro (입체구조적으로 안정화된 리포좀의 특성 및 혈장내 안정성)

  • 이지혜
    • YAKHAK HOEJI
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    • v.44 no.3
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    • pp.251-256
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    • 2000
  • Sterically stabilized liposomes (SSL) composed of distearoylphosphatidylcholine, cholesterol, dicetylphosphate and distearoylphosphatiodylethanolamine-N-poly(ethyleneglycol) 2000 (DSPE-PEG 2000) were made by reverse phase evaporation method to prolong biological half-life and decrease toxic side effect of drug. Streptozocin (572), a water-soluble antitumor agent with short half-life, was selected as a model drug. The size of SSL was controlled by polycarbonate extrusion to 100 nm which is adequate size for long circulation in plasma. The release rate of drugs from SSL in PBS was evaluated. And the stability of STZ-containing liposomes against drug leakage into rat plasma was evaluated in order to investigate the interaction of liposome and plasma protein. Incorporation of DSPE-PEG 2000 into conventional liposomes significantly decreased the drug leakage into rat plasma.

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Prediction of drug-Drug Interaction During Oral Absorption of Carrier-Mediated Compounds in Humans

  • Oh, Doo-Man;Gordon L. Amidon
    • Archives of Pharmacal Research
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    • v.17 no.5
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    • pp.364-370
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    • 1994
  • A microscopic mass balance approach has been developed to estimate the extent and rate of absorption for camier-mediated comounds. For the case competitive inhibition in the presence of an inhibitor which shares the same camier, the fraction dose absorbed (F) and absorption rate constant ($K_a$) of a drug can be calculated from its concentration profile in the intestinal lumen. Absorption parameters obtained by single-pass perfusion experiments were used in the simultaion of the absorption of some aminopenicilins. Predicted fractions dose absorbed and absorption rate constants of ampicilin and amoxicilin were significantly reduced in the presence of a 6-times higher molar dose of cyclacilin. The drug-drug interactions on the competitive absroption of camier-mediated compounds were determined with regard to F and $K_a$. Predicted decreases in F for some aminopenicilins corrlated well with decrease in the urinary recovery in humans reported in the literature. Predicted decrease in the mean absorption rate constant ($\barK_a$) explain the delays in the time of peak plasma concentration ($T_{max}$) reported in humans.

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Concomitant Medication by Multiple Prescriptions Causing Duplication and Severe drug Interaction: During DUR Pilot Projects in Goyangsi and Jejudo (다처방에 의한 의약품의 병용으로 인한 중복 및 병용금기의 문제: 고양시 및 제주도 DUR 시범사업을 중심으로)

  • Shin, Kwang-Shik
    • Korean Journal of Clinical Pharmacy
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    • v.21 no.2
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    • pp.106-114
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    • 2011
  • While multiple medication is an important global medication safety issue, ununified concomitant medication by multiple prescriptions may cause more severe problems by the fact that those are neither intended nor watched. This could cause therapy duplication and severe drug interaction and etc. Korean Government made region wide scale programs twice to detect such problems and give warnings to pharmacists and doctors through the internet system in 2009-2010, which are called Drug Use Review Services Pilot Project. This study is an analysis and comparison of the results of the two DUR pilot projects. There were 5.0 and 4.2 cases of severe drug interaction by the concomitant medication of multiple doctors' prescriptions per 10 thousand prescriptions, while only 0.37 and 0 cases by the medication of same doctor's prescription(s). There were 426 and 381 cases of drug duplication by the concomitant medication of multiple doctors' prescriptions per 10 thousand cases, while only 197 and 23 cases by medication of same doctors' prescription(s). Doctors' participation to those projects improved at Jejudo the later one compared to Goyangsi the former, which means the efforts of them to make less prescription problems succeeded to decrease the number of cases caused from same doctor's prescription. But they could not decrease the number of problem cases caused from concomitant medication by multiple doctors prescriptions enough. The findings support the issue of strengthening and widening the project nation wide and the issue of recommending the patients to designate their own pharmacy, which can provide them counseling for unified and safety controlled medication.

Use of Information Component (IC) and Relative Risk (RR) for Signal Detection of Drug Interactions of Clopidogrel : Data-mining Study Using Health Insurance Review & Assessment Service (HIRA) Claims Database (정보 성분과 상대위험도를 이용한 clopidogrel의 약물상호작용 시그널 검색 : 건강보험데이터베이스를 대상으로 한 데이터마이닝 연구)

  • Kim, Jin-Hyung;Choi, Chung-Am;Oh, Jung-Mi;Son, Sung-Ho;Shin, Wan-Gyoon
    • Korean Journal of Clinical Pharmacy
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    • v.21 no.2
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    • pp.90-99
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    • 2011
  • Health Insurance Review & Assessment Service (HIRA) claims database has a high potential to detect signals of new drug interactions. The aim of this study was to evaluate the usefulness of information component (IC) and relative risk (RR) as a tool for signal detection, and to analyze the possible drug interactions caused by clopidogrel using HIRA claims database. This study was performed in elderly patients over 65 years of age who administered clopidogrel from January 2005 to June 2006 in South Korea. Serious Adverse Events (SAEs) as drug interactions of clopidogrel were defined as any ambulatory hospitalization for ischemic diseases within comcomitant medication period of clopidogrel. Information Component (IC) and Relative Risk (RR) were calculated to compare the proportion of drug-SAE pairs in order to select drug specific SAEs. IC and RR signals of clopidogrel drug interaction were screened when IC's 95% confidence interval was greater than 0 and RR's 95% confidence interval was greater than 1 respectively. All detected signals were compared to references such as $Micromedex^{(R)}$ and 2010 Drug Interaction $Facts^{TM}$. Sensitivity, specificity, positive predicted value and negative predicted value were used to evaluate usefulness of this method. Among 13,252,930 cases of elderly patients who co-administered clopidogrel and other drugs, 47,485 cases were detected as SAE. Of these, one-hundred nine cases were detected by the IC-based data-mining approach and ninety one cases were detected by the RR-based data-mining approach. Total One-hundred sixty three unrecognized signals were detected by IC or RR. Twelve signals from IC-based data-mining (57.1%) were corresponded with drug interactions from references and eight signals from RR-based data-mining (38.1%) were corresponded with drug interactions from references. These signals include proton pump inhibitors, calcium channel blockers and HMG CoA reductase Inhibitors, which were known to affect CYP450 metabolism. Further studies using HIRA claims database are necessary to develop appropriate data-mining measure.

Fabrication and Characterization of Flurbiprofen loaded Chitosan Beads for Periodontal Regeneration (치주조직 재생용 플루르비프로펜 함유 키토산 비드의 제조 및 용출특성)

  • Rhee, Su-Jin;Park, Yoon-Jeong;Lee, Seung-Jin;Chung, Chong-Pyoung
    • Journal of Pharmaceutical Investigation
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    • v.27 no.1
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    • pp.71-77
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    • 1997
  • With the aim of improving periodontal regeneration efficacy, as a biodegradable local drug delivery device, drug releasing chitosan beads were prepared. Chitosan beads were prepared through the formation of intermolecular or intramolecular ionic interaction bewteen chitosan and sodium tripolyphosphate and were loaded with flurbiprofen. The mean diameter of the beads was $250\;{\mu}m$. Drug loading efficiency was improved by regulating the pH of tripolyphosphate solution. The drug release kinetics mainly depended upon the hydrophobic properties of the flurbiprofen, that is, the release of flurbiprofen showed initial burst with rapid release for the first day followed by a levelling off of the release rate. However, the release rate could be controlled by the formulation factor including the pH, concentration of the tripolyphosphate solution, gelation time, drug contents. From these results, flurbiprofen loaded chitosan beads were anticipated as biodegradable local drug delivery devices for periodontal regeneneration.

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Formulation and Evaluation of Transdermal Patch Containing Sibutramine

  • Subedi, Robhash Kusam;Jang, Jun-Ho;Kim, Jae-Il;Park, Young-Joon;Choi, Hoo-Kyun
    • Journal of Pharmaceutical Investigation
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    • v.40 no.1
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    • pp.33-38
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    • 2010
  • Sibutramine is a serotonin-norepinephrine reuptake inhibitor indicated for the management of obesity in conjunction with a reduced calorie diet. The oral administration of sibutramine is followed by its dose-related side effects. In this study, sibutramine was formulated into drug in adhesive (DIA) patches in an attempt to overcome these problems. The effects of different formulation variables including pressure-sensitive adhesive (PSA), loading amount of drug, thickness of matrix and enhancer on the skin permeation of the drug were evaluated using excised hairless mouse skin. In the acrylic adhesive with carboxyl functional group, low release of sibutramine was observed due to the strong interaction between carboxyl group of adhesive and amine group of sibutramine. The acrylic adhesive without functional group provided good adhesion force and allowed high drug loading. Changing drug load as well as thickness of the matrix was found to alter permeation rate. $Crovol^{(R)}$ PK40 and $Crovol^{(R)}$ A40, were found to be effective enhancers for sibutramine. The optimized patch contained 20% sibutramine, and 5% $Crovol^{(R)}$ A40 as permeation enhancer, in $80\;{\mu}m$ thick Duro-$Tak^{(R)}$ 87-9301 matrix.

Identifying literature-based significant genes and discovering novel drug indications on PPI network

  • Park, Minseok;Jang, Giup;Lee, Taekeon;Yoon, Youngmi
    • Journal of the Korea Society of Computer and Information
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    • v.22 no.3
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    • pp.131-138
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    • 2017
  • New drug development is time-consuming and costly. Hence, it is necessary to repurpose old drugs for finding new indication. We suggest the way that repurposing old drug using massive literature data and biological network. We supposed a disease-drug relationship can be available if signal pathways of the relationship include significant genes identified in literature data. This research is composed of three steps-identifying significant gene using co-occurrence in literature; analyzing the shortest path on biological network; and scoring a relationship with comparison between the significant genes and the shortest paths. Based on literatures, we identify significant genes based on the co-occurrence frequency between a gene and disease. With the network that include weight as possibility of interaction between genes, we use shortest paths on the network as signal pathways. We perform comparing genes that identified as significant gene and included on signal pathways, calculating the scores and then identifying the candidate drugs. With this processes, we show the drugs having new possibility of drug repurposing and the use of our method as the new method of drug repurposing.

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 Probenecid and Lithium Carbonate (프로베네시드와 탄산리튬의 약물상호작용)

  • Lee, Jin-Hwan;Lee, Chong-Ki
    • Journal of Pharmaceutical Investigation
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    • v.17 no.2
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    • pp.95-98
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    • 1987
  • The drug interaction between probenecid and lithium carbonate was studied pharmacokinetically in rabbits. The blood level and the area under the concentration curve (AUC) of lithium carbonate administered orally were elevated by coadministration of probenecid. Probenecid inhibited the urinary excretion of lithium carbonate in rabbits. Biological half-life and $t_{max}$ of lithium carbonate were prolonged by coadministration of probenecid. From these results, dosage regimen of lithium carbonate is considered to be adjusted for effective and safe therapy in the coadministration of probenecid.

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In Vitro Assessment of Cytochrome P450 Inhibition by Ambroxol and Cetirizine (암브록솔과 세티리진의 Cytochrome P450 저해 활성 평가)

  • Kim, Bong-Hee;Ryu, Chang Seon;Jang, Him Chan;Lee, Sang Yoon;Lee, Ji-Yoon;Chae, Jung-Woo;Kwon, Kwang-Il;Kim, Sang Kyum
    • YAKHAK HOEJI
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    • v.57 no.3
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    • pp.194-198
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    • 2013
  • In the present study we evaluated drug-drug interaction potential of ambroxol and cetirizine mediated by inhibition of CYP isoforms including CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4 using pooled human liver microsomes (HLMs). As measured by liquid chromatography-electrospray ionization tandem mass spectrometry, cetirizine and ambroxol inhibited significantly CYP2E1 but the maximal inhibition was approximately 36% at 10 ${\mu}M$ cetirizine and 28% at 3 ${\mu}M$ ambroxol. In addition, CYP2D6 activity was decreased to approximately 83% of control activity in pooled HLM incubated with 3 ${\mu}M$ ambroxol. Activities of CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, and CYP3A4 were not significantly inhibited by cetirizine and ambroxol. Considering their maximal plasma concentration in human ($C_{max}$ of cetirizine is approximately 0.67 ${\mu}M$ and $C_{max}$ of ambroxol is 0.044 ${\mu}M$), these two drugs have very low possibility in drug-drug interaction by CYP inhibition in clinical situations.