• Title/Summary/Keyword: Drug-interaction

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The Effects of Laminaria japonica Diet on the Pharmacokinetics of Metformin and Glucose Absorption in Rats (흰쥐에서 다시마 식이가 메트폴민의 체내동태 및 당 흡수에 미치는 영향)

  • Choi, Han-Gon;Jang, Bo-Hyun;Rhee, Jong-Dal;Kim, Jung-Ae;Yu, Bong-Kyu;Yong, Chul-Soon
    • Journal of Pharmaceutical Investigation
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    • v.33 no.3
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    • pp.171-178
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    • 2003
  • Drug interactions with food, on occasion, lead to serious nutritional and functional changes in the body as well as alterations of pharmacological effect. It, therefore, should be necessary to take drug interactions with food into consideration for effective and safe therapeutics. Diabetes mellitus is a heterogeneous group of disorders characterzed by abnormal glucose homeostasis, resulting in hyperglycemia, and is associated with increased risk of microvascular, macrovascular, and neuropathic complications. However, the precise mechanism of diabetes mellitus remains unclear. Three basic objectives in the care of diabetic patients are maintaining optimal nutrition, avoiding hypo- or hyperglycemia and preventing complications. Laminaria japonica is a brown macroalgae which can be used as a functional diet due to high content of diatery fiber. The purpose of this study was to investigate the effect of Laminaria japonica diet on the pharmacokinetics of metformin which are frequently used in the treatment of diabetes. Diabetic rats induced by streptozotocin were employed in this study. Blood concentrations of oral hypoglycemic agent, metformin, were measured by HPLC and resultant pharmacokinetic parameters were calculated by RSTRIP. The mechanisms of drug interaction with food were evaluated on the basis of pharmacokinetic parameters such as $k_{a},\;t_{1/2},\;C_{max},\;t_{max}$, and AUC. Administration of metformin in normal and diabetic rats treated with Laminaria japonica diet showed significant decrease in AUC, $C_{max},\;and\;k_a$, and increase in $t_{max}$, compared to those with normal diet. This might result from adsortion of metformin on components of Laminaria japonica, causing delayed absorption. The oral glucose test showed that Laminaria japonica diet could lower blood glucose level probably through either inhibiting the activity of disaccharidases, intestinal digestive enzymes, or delaying the absorption of glucose. More studies should be followed to fully understand pharmacokinetic changes of metformin caused by long-term Laminaria japonica diet.

The Effect of Laminaria japonica Diet on the Pharmacokinetics of Glipizide in Rats (다시마 식이가 흰쥐에서 글리피지드의 체내동태에 미치는 영향)

  • Choi, Han-Gon;Jang, Bo-Hyun;Rhee, Jong-Dal;Yu, Bong-Kyu;Yong, Chul-Soon
    • Journal of Pharmaceutical Investigation
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    • v.33 no.2
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    • pp.113-120
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    • 2003
  • Drug interactions with food, on occasion, lead to serious nutritional and functional changes in the body as well as alternations of pharmacological effect. It, therefore, should be necessary to take drug interactions with food into consideration for effective and safe therapeutics. Diabetes mellitus is a heterogeneous group of disorders characterized by abnormal glucose homeostasis, resulting in hyperglycemia, and is associated with increased risk of micovascular, macrovascular, and neuropathic complications. However, the precise mechanism of diabetes mellitus remains unclear. Three basic objectives in the care of diabetic patients are maintaining optimal nutrition, avoiding hypo- or hyperglycemia and preventing complications. The purpose of this study was to investigate thε effect of Laminaria japonica diet on the absorption, distribution, metabolism and excretion of glipizide which are frequently used in the treatment of diabetes. Diabetic rats induced by streptozotocin were employed in this study. Blood concentrations of oral hypoglycemic agents were measured by HPLC and resultant pharmacokinetic parameters were calculated by RSTRIP. The mechanisms of drug interaction with food were evaluated on the basis of pharmacokinetic parameters such as $k_{a},\;t_{1/2},\;C_{max},\;t_{max}$ and AUC. Administration of glipizide in normal rats treated with Laminaria japonica diet showed significant increase in AUC, $k_{a},\;t_{1/2},\;t_{max}$ and decrease in $C_{max}$, compared to those without Laminaria japonica diet. This might result from adsorption of glipizide on components of Laminaria japonica, causing delayed absorption. Administration of glipizide in diabetic rats treated with Laminaria japonica diet showed significant increase in $t_{1/2}\;and\;t_{max}$, and decrease in $C_{max}$, compared to those without Laminaria japonica diet. This might also result from adsorption of glipizide on components of Laminaria japonica, causing delayed absorption and flattened blood concentration of glipizide. The oral glucose test showed that Laminaria japonica diet could lower blood glucose level probably through either inhibiting the activity of disaccharidases, intestinal digestive enzymes, or delaying the absorption of glucose. More studies should be followed to fully understand pharmacokinetic changes of glipizide caused by long-term Laminaria japonica diet.

Evaluation of Prescription Data for Development of Warfarin Nomogram in Korean Patients with Cerebral Infarction (뇌졸중 환자군의 Warfarin Nomogram 설정을 위한 실제 처방전 평가)

  • Jang, Ju-Young;Ko, Kyung-Mi;Yoon, Ji-Yeon;Han, Ok-Yeon;Lim, Sung-Cil
    • YAKHAK HOEJI
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    • v.53 no.2
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    • pp.83-88
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    • 2009
  • Warfarin is the most widely used oral anticoagulant in the world but maintenance of proper therapeutic range and prevention of adverse drug events always need to be careful. Especially, in Korea, warfarin dosing for patients with cerebral infarction is currently based on the nomogram which is done by foreign clinical trials not for the Korean. Therefore we evaluate warfarin dose of patients in the neurology and eventually get the base data of warfarin nomogram for Korean with stroke. We performed this study retrospectively on reviewing the medical charts to evaluate the prescribed loading dose (LD) and maintenance dose (MD) of warfarin and each responding International Normalized Ratio (INR) with any bleeding adverse drug reaction including of patient's characteristics for total 75 patients with stroke in the department of neurology of Kangnam ST. Mary's Hospital from January 2005 to June 2008. All evaluated patients should not be treated with warfarin in the past at all and should be initiated warfarin therapy first.ly at this time. All evaluated patients were divided as two classes by wafarin LD which is; 1) HDG - a high loading dosing group prescribed over 5mg, and 2) LDG - a low loading dosing group prescribed 5mg or below. As a result, average LD was $9.34{\pm}0.22$ mg (p=0.000) in HDG and $4.25{\pm}0.39$ mg (p=0.000) in LDG. Average baseline INR was $0.91{\pm}0.05$ (p=0.161) in HDG and $1.26{\pm}0.14$ (p=0.002) in LDG. On the first and second week, daily MD was $4.21{\pm}0.14$ mg (p=0.000) and $2.96{\pm}0.19$ mg (p=0.696) in HDG and also in LDG, $2.95{\pm}0.29$ mg (p=0.000) and $3.14{\pm}0.36$ mg (p=0.696). Also average reacting daily INR was respectively $2.53{\pm}0.12$ (p=0.141) and $2.51{\pm}0.16$ (p=0.678) in HDG, and in LDG, $2.11{\pm}0.17$ (p=0.141) and $2.42{\pm}0.14$ (p=0.678). After the second week, INR was not measured in regularly. Also most of underlying diseases were hypertension (n=38), diabetes mellitus (n=14), dyslipidemia (n=8) in order. Four ADRs with simple hemorrhage were occurred and those were due to drug interaction by comedication. In the conclusion, proper starting LD for Korean with stroke is 10 mg if baseline INR is around 1.0 or 5 mg if over 1.3. Proper MD need to be more evaluated in the future for setting up warfarin nomogram to make prospective study.

The current status of the combination therapy of frequently used herbal extracts and anti-platelet drug, anti-coagulant drug in ischemic stroke patients hospitalized in oriental medical hospital (한방병원 입원 허혈성 뇌경색 환자에서 한방 의료보험용 엑스산제와 항혈소판제 및 항응고제의 병용투여 현황)

  • Han, Su-Ryun;Park, Sung-Hwan;Ahn, Young-Min;Ahn, Se-Young;Lee, Byung-Cheol
    • The Journal of Korean Medicine
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    • v.32 no.2
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    • pp.14-22
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    • 2011
  • Objective: Nowadays the combined use of herbal extracts and western medicines has been prevalent, but concern about its risk is also increasing. Even though the importance of clinical trials is well recognized, there have been only a few studies on the combined use of herbal extracts and western medicines. This study was aimed to examine which herbal extracts and antiplatelets or anticoagulants are most commonly prescribed together to inpatient ischemicstroke patients and investigate the combined prescription rate. Methods: We investigated the most frequently prescribed herbal extracts from two different sources. First, we chose herbal medicine extracts from 2008 Traditional Korean Medicine Utilization Status. Then, among patients who were admitted to Kyung-Hee Oriental Medical Center diagnosed with ischemic stroke, we found patients who were administered with these herbal medicine extracts and among these patients, we investigated how many were concomitantly administered with antiplatelets or anticoagulants. Second, we chose other herbal medicine extracts that were most often prescribed within Kyung-Hee Oriental Medical Center and found patients who were administered with these herbal medicine extracts, then investigated how many of them were concomitantly administered with specific antiplatelets or anticoagulants. Results: The most commonly prescribed herbal medicine extracts among ischemic stroke patients were Ojeok-san, Bojungikgi-tang, Sochungryong-tang and Samsoeum. About 46 to 69 percent were concomitantly administered with either specific antiplatelets or anticoagulants. Conclusions: The most often prescribed herbal medicine extracts in inpatient ischemic stroke patients are Ojeok-san, Bojungikgi-tang, Sochungryong-tang, and Samsoeum. Among patients who were prescribed with Ojeok-san, Bojungikgi-tang, Sochungryong-tang, Samsoeum, patients who were concomitantly administered with either antiplatelets or anticoagulants were about 46% to 69%.

Effects of Some Crude Drug Extracts on the Brain Neurotransmitters in the Ethanol-Treated Rats (수종의 생약 추출물이 에탄올 투여 흰쥐의 뇌 부위별 신경전달물질에 미치는 영향)

  • Linh, Pham-Tuan;Lee, Soon-Chul;Kim, Young-Ho;Hong, Seon-Pyo;Song, Chang-Woo;Kang, Jong-Seong
    • Analytical Science and Technology
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    • v.13 no.5
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    • pp.630-635
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    • 2000
  • The concentration of neurotransmitters in rat brain was determined by HPLC-ECD (electrochemical detection) method and the effects of methanol extracts of some crude drugs, such as Polygala Radix, Myristicae Semen, Zizyphi Semen, Acori graminei Rhizoma, Visci Herba, Liriopsis Tuber, Myrrha on the concentration of neurotransmitters in the ethanol-treated rat brain were investigated. By the administration of ethanol, dopamine (DA), 3, 4-dihydroxyphenyl acetic acid (DOPAC) and serotonin (5-HT) levels in frontal cortex and 5-HT level in hippocampus were significantly increased compared with the neurotransmitter levels in the brain of saline-treated rats. The ${\gamma}$-aminobutyric acid (GABA) level in frontal cortex was decreased by the same treatment. There was a tendency that the DA level in frontal cortex and striatum of ethanol-treated rats were increased by the administration of crude drug extracts. Especially, Myrrha and Visci Herba significantly increased the DA level of frontal cortex in ethanol-treated rats, while they significantly decreased the 5-HT level in the same region of the brain. GABA level in striatum of ethanol-treated rats was significantly decreased by Myristicae Semen, Visci Herba and Myrrha. These results suggest that the tested crude drug extracts have selective interaction with neurotransmitters in specified region of central nervous system.

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Inhibition of DNA-dependent Protein Kinase by Blocking Interaction between Ku Complex and Catalytic Subunit of DNA-dependent Protein Kinase

  • Kim, Chung-Hui;Cuong, Dang-Van;Kim, Jong-Su;Kim, Na-Ri;Kim, Eui-Yong;Han, Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.7 no.1
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    • pp.9-14
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    • 2003
  • Recent studies indicated that cancer cells become resistant to ionizing radiation (IR) and chemotherapy drugs by enhanced DNA repair of the lesions. Therefore, it is expected to increase the killing of cancer cells and reduce drug resistance by inhibiting DNA repair pathways that tumor cells rely on to escape chemotherapy. There are a number of key human DNA repair pathways which depend on multimeric polypeptide activities. For example, Ku heterodimer regulatory DNA binding subunits (Ku70/Ku80) on binding to double strand DNA breaks (DSBs) are able to interact with 470-kDa DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and are essential for DNA-dependent protein kinase (DNA-PK) activity. It has been known that DNA-PK is an important factor for DNA repair and also is a sensor-transmitting damage signal to downstream targets, leading to cell cycles arrest. Our ultimate goal is to develop a treatment of breast tumors by targeting proteins involved in damage-signaling pathway and/or DNA repair. This would greatly facilitate tumor cell cytotoxic activity and programmed cell death through DNA damaging drug treatment. Therefore, we designed a domain of Ku80 mutants that binds to Ku70 but not DNA end binding activity and used the peptide in co-therapy strategy to see whether the targeted inhibition of DNA-PK activity sensitized breast cancer cells to irradiation or chemotherapy drug. We observed that the synthesized peptide (HNI-38) prevented DNA-PKcs from binding to Ku70/Ku80, thus resulting in inactivation of DNA-PK activity. Consequently, the peptide treated cells exhibited poor to no DNA repair, and became highly sensitive to IR or chemotherapy drugs, and the growth of breast cancer cells was inhibited. Additionally, the results obtained in the present study also support the physiological role of resistance of cancer cells to IR or chemotherapy.

Surface Chemistry in Biocompatible Nanocolloidal Particles (생체 적합한 나노입자와 계면화학)

  • Kim Jong-Duk;Jung Jae Hyun
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.30 no.3 s.47
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    • pp.295-305
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    • 2004
  • Colloid and surface chemistry have been focused on surface area and surface energy. Local surface properties such as surface density, interaction, molecular orientation and reactivity have been one of interesting subjects. Systems of such surface energy being important would be listed as association colloid, emulsion, particle dispersion, foam, and 2-D surface and film. Such nanoparticle systems would be applied to drug delivery systems and functional cosmetics with biocompatible and degradable materials, while nanoparticles having its size of several nm to micron, and wide surface area, have been accepted as a possible drug carrier because their preparation, characteristics and drug loading have been inves-tigated. The biocompatible carriers were also used for the solubilization of insoluble drugs, the enhancement of skin absorption, the block out of UV radiation, the chemical stabilization and controlled release. Nano/micro emulstion system is classified into nano/microsphere, nano/microcapsule, nano/microemulsion, polymeric micelle, liposome according to its prep-aration method and size. Specially, the preparation method and industrial applications have been introduced for polymeric micelles self-assembled in aqueous solution, nano/microapsules controlling the concentration and activity of high concen-tration and activity materials, and monolayer or multilayer liposomes carrying bioactive ingredients.

Algicidal Characteristics of Cashew Nut Oil against Microalgae and Development of its Mixtures with Synergistic Effects (미세조류에 대한 캐슈넛 오일의 살조활성특징과 상승효과를 가지는 혼합처리제 탐색)

  • Kwak, Hwa Sook;Kim, Bo Gwan;Kim, Jin-Seog
    • Weed & Turfgrass Science
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    • v.5 no.3
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    • pp.136-143
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    • 2016
  • This study was conducted to investigate the algicidal characteristics of cashew nut oil (CNO) and to develop CNO mixtures with other compounds having synergistic effects on the growth inhibition against a blue-green alga, Microcystis aeruginosa. Among tested CNOs, CNO with higher anacardic acid contents (Ana-A) exhibited the best algicidal activity against M. aeruginosa. Ana-A showed broad algicidal spectrum with particular greater activity against blue-green algae than green algae. Ana-A showed the greatest activity against to Oscillatoria tenuis ($IC_{50}=0.19{\mu}g\;mL^{-1}$) among the tested blue-green algae and to Chlorella vulgaris ($IC_{50}=4.54{\mu}g\;mL^{-1}$) among the tested green algae, respectively. In a mixture experiment to evaluate a chemical interaction in M. aeruginosa control, Ana-A showed a strong synergistic effect with MSB and menadione, mild synergistic effect with citric acid, and additive effect with chryspophanol, copper sulfate and quinoclamine. Taken together, our results suggest that CNO containing higher anacardic acid can be used as an eco-friendly natural algicide for selective control of blue-green algae such as M. aeruginosa and O. tenuis through an optimization of application rate and in combination with synergists such as MSB and menadione.

Target engagement of ginsenosides in mild cognitive impairment using mass spectrometry-based drug affinity responsive target stability

  • Zhu, Zhu;Li, Ruimei;Qin, Wei;Zhang, Hantao;Cheng, Yao;Chen, Feiyan;Chen, Cuihua;Chen, Lin;Zhao, Yunan
    • Journal of Ginseng Research
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    • v.46 no.6
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    • pp.750-758
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    • 2022
  • Background: Mild cognitive impairment (MCI) is a transitional condition between normality and dementia. Ginseng is known to have effects on attenuating cognitive deficits in neurogenerative diseases. Ginsenosides are the main bioactive component of ginseng, and their protein targets have not been fully understood. Furthermore, no thorough analysis is reported in ginsenoside-related protein targets in MCI. Methods: The candidate protein targets of ginsenosides in brain tissues were identified by drug affinity responsive target stability (DARTS) coupled with label-free liquid chromatography-mass spectrometry (LC-MS) analysis. Network pharmacology approach was used to collect the therapeutic targets for MCI. Based on the above-mentioned overlapping targets, we built up a proteineprotein interaction (PPI) network in STRING database and conducted gene ontology (GO) enrichment analysis. Finally, we assessed the effects of ginseng total saponins (GTS) and different ginsenosides on mitochondrial function by measuring the activity of the mitochondrial respiratory chain complex and performing molecular docking. Results: We screened 2526 MCI-related protein targets by databases and 349 ginsenoside-related protein targets by DARTS. On the basis of these 81 overlapping genes, enrichment analysis showed the mitochondria played an important role in GTS-mediated MCI pharmacological process. Mitochondrial function analysis showed GTS, protopanaxatriol (PPT), and Rd increased the activities of complex I in a dose-dependent manner. Molecular docking also predicted the docking pockets between PPT or Rd and mitochondrial respiratory chain complex I. Conclusion: This study indicated that ginsenosides might alleviate MCI by targeting respiratory chain complex I and regulating mitochondrial function, supporting ginseng's therapeutic application in cognitive deficits.

Modeling Growth Kinetics of Lactic Acid Bacteria for Food Fermentation

  • Chung, Dong-Hwa;Kim, Myoung-Dong;Kim, Dae-Ok;Koh, Young-Ho;Seo, Jin-Ho
    • Food Science and Biotechnology
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    • v.15 no.5
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    • pp.664-671
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    • 2006
  • Modeling the growth kinetics of lactic acid bacteria (LAB), one of the most valuable microbial groups in the food industry, has been actively pursued in order to understand, control, and optimize the relevant fermentation processes. Most modeling approaches have focused on the development of single population models. Primary single population models provide fundamental kinetic information on the proliferation of a primary LAB species, the effects of biological factors on cell inhibition, and the metabolic reactions associated with cell growth. Secondary single population models can evaluate the dependence of primary model parameters, such as the maximum specific growth rate of LAB, on the initial external environmental conditions. This review elucidates some of the most important single population models that are conveniently applicable to the LAB fermentation analyses. Also, a well-defined mixed population model is presented as a valuable tool for assessing potential microbial interactions during fermentation with multiple LAB species.