• Title/Summary/Keyword: drug combinations

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Antimicrobial Drug Release Scaffolds of Natural and Synthetic Biodegradable Polymers

  • Prabu, Periasamy;Kim, Kwan-Woo;Dharmaraj, Nallusamy;Park, Jong-Hoon;Khil, Myung-Seob;Kim, Hak-Yong
    • Macromolecular Research
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    • v.16 no.4
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    • pp.303-307
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    • 2008
  • A series of biodegradable polymeric scaffolds was prepared by using a combination of natural (collagen) and synthetic (poly(caprolactone)) (PCL) polymers in various compositions. These scaffolds were soft, spongy, porous and transparent in nature and were characterized by thermogravimetric analysis (TGA) and Fourier transform infrared (FT-IR) spectroscopy. The entrapment efficiency and drug release activity of the scaffolds were analyzed using penicillin and tetracycline as antimicrobial drugs. The drug release activity of the scaffolds with various combinations of collagen and PCL were studied by measuring the optical density in a spectrophotometer at the following time intervals: 1,4, 24, 48 and 60 h. These scaffolds showed better and continuous drug release for up to 60 h. Even after such a long duration, a portion of the drug remained entrapped in the scaffolds, indicating that they can be utilized for wound healing applications.

Immune Activation by siRNA/Liposome Complexes in Mice Is Sequence- independent: Lack of a Role for Toll-like Receptor 3 Signaling

  • Kim, Ji Young;Choung, Sorim;Lee, Eun-Ju;Kim, Young Joo;Choi, Young-Chul
    • Molecules and Cells
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    • v.24 no.2
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    • pp.247-254
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    • 2007
  • Improvement in the pharmacokinetic properties of short interfering RNAs (siRNAs) is a prerequisite for the therapeutic application of RNA interference technology. When injected into mice as unmodified siRNAs complexed to DOTAP/Chol-based cationic liposomes, all 12 tested siRNA duplexes caused a strong induction of cytokines including interferon ${\alpha}$, indicating that the immune activation by siRNA duplexes is independent of sequence context. When modified by various combinations of 2'-OMe, 2'-F, and phosphorothioate substitutions, introduction of as little as three 2'-OMe substitutions into the sense strand was sufficient to suppress immune activation by siRNA duplexes, whereas the same modifications were much less efficient at inhibiting the immune response of single stranded siRNAs. It is unlikely that Toll-like receptor 3 (TLR3) signaling is involved in immune stimulation by siRNA/liposome complexes since potent immune activation by ds siRNAs was induced in TLR3 knockout mice. Together, our results indicate that chemical modification of siRNA provides an effective means to avoid unwanted immune activation by therapeutic siRNAs. This improvement in the in vivo properties of siRNAs should greatly facilitate successful development of siRNA therapeutics.

An experience on the model-based evaluation of pharmacokinetic drug-drug interaction for a long half-life drug

  • Hong, Yunjung;Jeon, Sangil;Choi, Suein;Han, Sungpil;Park, Maria;Han, Seunghoon
    • The Korean Journal of Physiology and Pharmacology
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    • v.25 no.6
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    • pp.545-553
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    • 2021
  • Fixed-dose combinations development requires pharmacokinetic drugdrug interaction (DDI) studies between active ingredients. For some drugs, pharmacokinetic properties such as long half-life or delayed distribution, make it difficult to conduct such clinical trials and to estimate the exact magnitude of DDI. In this study, the conventional (non-compartmental analysis and bioequivalence [BE]) and model-based analyses were compared for their performance to evaluate DDI using amlodipine as an example. Raw data without DDI or simulated data using pharmacokinetic models were compared to the data obtained after concomitant administration. Regardless of the methodology, all the results fell within the classical BE limit. It was shown that the model-based approach may be valid as the conventional approach and reduce the possibility of DDI overestimation. Several advantages (i.e., quantitative changes in parameters and precision of confidence interval) of the model-based approach were demonstrated, and possible application methods were proposed. Therefore, it is expected that the model-based analysis is appropriately utilized according to the situation and purpose.

Patterns of Over-the-Counter Drug Use and Interactions between Over-the-Counter Drugs and Prescription Drugs in Adults Visiting a Community Pharmacy (지역약국 방문 성인의 일반의약품 복용실태 및 일반의약품과 처방의약품과의 상호작용 연구)

  • Chae, Min Kyoung;Bang, Joon Seok;Lee, Yu Jeung
    • Korean Journal of Clinical Pharmacy
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    • v.23 no.1
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    • pp.49-56
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    • 2013
  • Objective: The purpose of this study was to evaluate the patterns of Over-the-Counter (OTC) drugs and their interactions with prescription drugs in adults visiting a community pharmacy. Method: The subjects were 151 adults aged over 20 years visiting a community pharmacy in Asan-si from December 16th 2011 to February 1st 2012. We used a survey questionnaire. The survey inquired about the prevalence and the details of any OTC drug use and the characteristics of the study subjects. The drug interaction classification system from Lexicomp's Lexi-interact data fields was used to identify OTC drugs likely to have clinically significant interactions with prescription drugs. Results: The patterns of OTC drug use were related to thirties (from 30 to 40 years old), female gender, higher education, non-smoking, sometimes use of alcohol, and self-perceived normal health status. The most commonly used OTC drug category was antipyretic-analgesics (n=104, 53.3%), and the most commonly used ingredient was acetaminophen (n=67, 64.4%). The biggest motivation for taking OTC drugs was suggestion by pharmacists, reported by 55.6%. After reviewing each patient's prescription drugs and OTC drugs, 14 patients (36.8%) of 38 patients using prescription drugs were taking drug combinations with potential for clinically significant interactions. The concomitant use of OTC drugs with prescription drugs may lead to increased potentially harmful interactions. Conclusion: It is suggested that health-care professionals should be more aware of the potential and possible interactions and take into better account their patients' OTC drug use.

Screening and Isolation of Antibiotic Resistance Inhibitors from Herb Materials-Resistance Inhibition of Volatile Components of Korean Aromatic Herbs

  • Lee, Chung-Kyu;Kim, Hye-Kyung;Moon, Kyung-Ho;Shin, Kuk-Hyun
    • Archives of Pharmacal Research
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    • v.21 no.1
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    • pp.62-66
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    • 1998
  • The resistance inhibitory activities of 54 odorant mixtures (essential oil) from 41 Korean aromatic herbs were tested against multi-drug resistant Staphylococcus aureus SA2, which has resistances to 10 usual antibiotics including chloramphenicol. As results, combinations of 28 kinds of samples from 21 herbs and chloramphenicol have resistance inhibitory activities in dose dependent manner.

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Factors Affecting the Rate of Release of 5-Fluorouracil from Ethylene-Vinyl Acetate Matrices

  • Oh, Seaung-Youl;Chung, Hee-Won;Cho, Sun-Hang;Lee, Hai-Bang
    • Journal of Pharmaceutical Investigation
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    • v.24 no.3
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    • pp.33-39
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    • 1994
  • We have studied the effect of loading amount and particle size on the rate of release of 5-fluorouracil (5-FU) from ethylene-vinyl acetate (EVA) matrix. Release rate increased as the loading amount and particle size increase. We also studied the effect of additives (lactose and algin) on the rate of release of 5-FU. Both algin and lactose promoted the rate of release. The ability to increase the rate is in the order of algin>lactose>5-FU. Scanning electron microscope study clearly shows that large cavities and cracks are created. The results imply that, by the proper combinations of the amount of the additive, $EVA_c$ and drug, the rate of drug release can be modulated over a wide range of values.

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The Screening of Antibiotics Resistance Inhibition of Herb Drugs entered in Korean Official Formulary (II) - Resistance Inhibition of 36 Essential Oils - (공정서 수재생약 정유의 항생제 내성억제작용 검색 (II) - 36종 정유의 내성억제작용 -)

  • Kim, Dong-Myeong;Heo, Kyung-Hee;Moon, Kyung-Ho;Lee, Chung-Kyu
    • Korean Journal of Pharmacognosy
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    • v.40 no.1
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    • pp.70-76
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    • 2009
  • Thirty six essential oils from herb drugs entered in Korean official formulary, which are frequently used in oriental region, were tested for antibiotic resistance inhibition. When the oils were combined with ampicillin (Am) or amoxicillin (Amx) they showed significant inhibitory effects on the growth of multi-drug resistant Staphylococcus aureus SA2 in considerably low concentration. The most effective combinations were oils from Acanthopanacis Cortex ($0.49{\mu}g/mL$) with Am and Cnidii Rhizoma and Lonicerae Flos (2.77 and $2.79{\mu}g/mL$, respectively) with Amx as shown in minimum resistance inhibitory concentrations.

Antimicrobial choice of severe endodontic infection (심한 근관 감염에서의 항생제 선택)

  • Cho, Ju-Yeon;Ha, Jung-Hong;Jin, Myoung-Uk;Kim, Young-Kyung;Kim, Sung-Kyo
    • The Journal of the Korean dental association
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    • v.52 no.7
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    • pp.425-431
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    • 2014
  • Objectives : The purpose of our study was to evaluate penicillin as a still drug of choice for severe endodontic infection, by analyzing the antimicrobial susceptibilities from endodontic infections with swelling to figure out appropriate antibiotics as empirical treatment. Materials and methods : This study involved 18 patients who attended for emergency treatment because of facial or periapical swelling associated with root canal infections. Identification and antimicrobial susceptibility test of each pathogen were performed by Vitek2 Systems (bioM$\acute{e}$rieux, Marcy l'Etoile, France). Results : The most frequent bacteria was Streptococcus spp.(77%), and the resistance against penicillin was 35% in overall patients, followed by clindamycin and erythromycin (17%), which was much higher than previous studies. Conclusions : In our study, the higher resistance made penicillin alone not to be chosen as the first antibiotic drug for severe endodontic infections. Combinations with other drug, penicillin with wider spectrum of activity, or changing to other antibiotics was considered while remembering the increased risk of resistant microorganism.

Effects of Non-Cytotoxic Concentration of Anticancer Drugs on Doxorubicin Cytotoxicity in Human Breast Cancer Cell Lines

  • Lee, Yoon-Ik;Lee, Young-Ik
    • BMB Reports
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    • v.29 no.4
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    • pp.314-320
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    • 1996
  • The effects of non-cytotoxic concentrations of tamoxifen, verapamil, and trifluoperazine on doxorubicin cytotoxicity in five human breast cancer cell lines were studied. A non-cytotoxic concentration of tamoxifen resulted in enhanced doxorubicin cytotoxicity in HTB-123, HTB-26, and MCF-7. In these three cell lines, a combination of tamoxifen with verapamil resulted in even more increased doxorubicin cytotoxicity. Addition of verapamil or trifluoperazine alone did not influence the doxorubicin cytotoxicity significantly. Only in HTB-19 did coincubation with verapamil increase the doxorubicin cytotoxicity. In HTB-123, combination of tamoxifen with trifluoperazine increased the doxorubicin cytotoxicity significantly. In the cell lines where co-incubation with tamoxifen increased doxorubicin sensitivity, high estrogen receptor expression was detected. However, HTB-20, where tamoxifen did not enhance doxorubicin action, was also estrogen receptor positive. None of the cell lines had multidrug resistance related drug efflux and drug retention was not increased by the treatment with tamoxifen and verapamil. Cell cycle traverses were not altered by incubation with tamoxifen, verapamil or combinations thereof. These observatlons suggest mechanism of non-cytotoxic concentrations of tamoxifen and verapamil on doxorubicin cytotoxicity may involve one or more other cellular processes besides those of interference of estrogen binding to its receptor, cell cycle perturbation, or drug efflux blocking.

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Clinical and pharmacological application of multiscale multiphysics heart simulator, UT-Heart

  • Okada, Jun-ichi;Washio, Takumi;Sugiura, Seiryo;Hisada, Toshiaki
    • The Korean Journal of Physiology and Pharmacology
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    • v.23 no.5
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    • pp.295-303
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    • 2019
  • A heart simulator, UT-Heart, is a finite element model of the human heart that can reproduce all the fundamental activities of the working heart, including propagation of excitation, contraction, and relaxation and generation of blood pressure and blood flow, based on the molecular aspects of the cardiac electrophysiology and excitation-contraction coupling. In this paper, we present a brief review of the practical use of UT-Heart. As an example, we focus on its application for predicting the effect of cardiac resynchronization therapy (CRT) and evaluating the proarrhythmic risk of drugs. Patient-specific, multiscale heart simulation successfully predicted the response to CRT by reproducing the complex pathophysiology of the heart. A proarrhythmic risk assessment system combining in vitro channel assays and in silico simulation of cardiac electrophysiology using UT-Heart successfully predicted drug-induced arrhythmogenic risk. The assessment system was found to be reliable and efficient. We also developed a comprehensive hazard map on the various combinations of ion channel inhibitors. This in silico electrocardiogram database (now freely available at http://ut-heart.com/) can facilitate proarrhythmic risk assessment without the need to perform computationally expensive heart simulation. Based on these results, we conclude that the heart simulator, UT-Heart, could be a useful tool in clinical medicine and drug discovery.