• Title/Summary/Keyword: Drug Distribution

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A Potential Role of Oxytocin and Acupuncture in Drug Addiction (옥시토신의 약물중독에서 역할과 침(鍼) 관련성)

  • Yang, Chae-Ha;Choi, Seong-Hun
    • Korean Journal of Oriental Medicine
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    • v.15 no.3
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    • pp.53-61
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    • 2009
  • Oxytocin(OT), classically known to stimulate labour and milk ejection, contributes to play an important role in a wide range of behavioral effects including drug addiction. An increasing body of evidence suggests that OT ameliorates acute and long-term effects of commonly used drugs by means of interacting with the mesolimbic dopamine system. Mesolimbic dopamine system is thought to play a major role in the reinforcing properties of drug abuse. Oxytocin receptors in the nucleus accumbens(NAc) and ventral tegmental area(VTA) have been implicated in the regulation of reinforcing effects in abused drugs. In the same way acupuncture may attenuate the reinforcing effects of abused drugs in the NAc and VTA. We have an interest in similar liaison between the substrates of acupuncture and drug addiction that may involve OT. Here, we described the possibility that acupuncture modulates the reinforcing and sensitizing properties of abused drugs in the dopaminergic system via the regulation of activities in the oxytocinergic system. The elements in this paper are summarized as follows : neuroanatomical studies of oxytocinergic innervation and distribution of oxytocin receptors; experiments related to the methamphetamine, cocaine, morphine and ethanol; experiments related to the oxytocin and acupuncture.

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The Transport of Organic Cations in the Small Intestine: Current Knowledge and Emerging Concepts

  • Kim, Moon-Kyoung;Shim, Chang-Koo
    • Archives of Pharmacal Research
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    • v.29 no.7
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    • pp.605-616
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    • 2006
  • A wide variety of drugs and endogenous bioactive amines are organic cations (OCs). Approximately 40% of all conventional drugs on the market are OCs. Thus, the transport of xenobiotics or endogenous OCs in the body has been a subject of considerable interest, since the discovery and cloning of a family of OC transporters, referred to as organic cation transporter (OCTs), and a new subfamily of OCTs, OCTNs, leading to the functional characterization of these transporters in various systems including oocytes and some cell lines. Organic cation transporters are critical in drug absorption, targeting, and disposition of a drug. In this review, the recent advances in the characterization of organic cation transporters and their distribution in the small intestine are discussed. The results of the in vitro transport studies of various OCs in the small intestine using techniques such as isolated brush-border membrane vesicles, Ussing chamber systems and Caco-2 cells are discussed, and in vivo knock-out animal studies are summarized. Such information is essential for predicting pharmacokinetics and pharmacodynamics and in the design and development of new cationic drugs. An understanding of the mechanisms that control the intestinal transport of OCs will clearly aid achieving desirable clinical outcomes.

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.

Evaluation of Usefulness of the Protein Drug Feature Information Filed (단백질 의약품 특성정보필드 유용성 평가)

  • Byeon, Jaehee;Choi, Yoo-Joo;Lee, Ju-Hwan;Suh, Jung-Keun
    • Journal of Internet Computing and Services
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    • v.15 no.4
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    • pp.21-31
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    • 2014
  • As the protein drug industry is growing, protein informations are indispensable for the protein drug development. NCBI and PDB in the U.S., the EMBL in Europe and the DDBJ in Japan are the representative centers for bio information and each center provides specific data for protein information. To obtain specific protein information, users are to be collect them from the service sites of each center and then combine or analyze for their purpose. To facilitate the accessibility to bio data, various R&D activities are running for development of diverse web services relevant to bio data in major data centers or small-scale projects. With the recognition of protein information as pivotal for the protein drug development, DrugBank in Canada, GDSC in the U.S. start to provide integrated informations between drugs and proteins. However, those service does not meet users' demands due to lack of diversity. In Korea, infra structures for bioinformatics are limited and the current services for protein drug information are providing only basic information of the drug including distribution data. This is a pilot study to construct a specialized service for protein drug information in Korean style breaking through the limitations of current services. This study proposed new fields for protein characterization information which had not been provided by current services and evaluated their effectiveness and usability by comparing them to the existing fields with expert survey. As a result, the newly proposed fields for protein characterization have been proven to be useful data fields for the service of protein drug information.

Ginsenoside Rb1 exerts neuroprotective effects through regulation of Lactobacillus helveticus abundance and GABAA receptor expression

  • Chen, Huimin;Shen, Jiajia;Li, Haofeng;Zheng, Xiao;Kang, Dian;Xu, Yangfan;Chen, Chong;Guo, Huimin;Xie, Lin;Wang, Guangji;Liang, Yan
    • Journal of Ginseng Research
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    • v.44 no.1
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    • pp.86-95
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    • 2020
  • Background: Ginsenoside Rb1 (Rb1), one of the most abundant protopanaxadiol-type ginsenosides, exerts excellent neuroprotective effects even though it has low intracephalic exposure. Purpose: The present study aimed to elucidate the apparent contradiction between the pharmacokinetics and pharmacodynamics of Rb1 by studying the mechanisms underlying neuroprotective effects of Rb1 based on regulation of microflora. Methods: A pseudo germ-free (PGF) rat model was established, and neuroprotective effects of Rb1 were compared between conventional and PGF rats. The relative abundances of common probiotics were quantified to reveal the authentic probiotics that dominate in the neuroprotection of Rb1. The expressions of the gamma-aminobutyric acid (GABA) receptors, including GABAA receptors (α2, β2, and γ2) and GABAB receptors (1b and 2), in the normal, ischemia/reperfusion (I/R), and I/R+Rb1 rat hippocampus and striatum were assessed to reveal the neuroprotective mechanism of Rb1. Results: The results showed that microbiota plays a key role in neuroprotection of Rb1. The relative abundance of Lactobacillus helveticus (Lac.H) increased 15.26 fold after pretreatment with Rb1. I/R surgery induced effects on infarct size, neurological deficit score, and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) were prevented by colonizing the rat gastrointestinal tract with Lac.H (1 × 109 CFU) by gavage 15 d before I/R surgery. Both Rb1 and Lac.H upregulated expression of GABA receptors in I/R rats. Coadministration of a GABAA receptor antagonist significantly attenuated neuroprotective effects of Rb1 and Lac.H. Conclusion: In sum, Rb1 exerts neuroprotective effects by regulating Lac.H and GABA receptors rather than through direct distribution to the target sites.

Computational Analysis of Airflow in Upper Airway for Drug Delivery of Asthma Inhaler (천식 흡입기의 약물전달을 위한 상기도내의 유동해석)

  • Lee, Gyun-Bum;Kim, Sung-Kyun
    • Transactions of the KSME C: Technology and Education
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    • v.2 no.2
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    • pp.73-80
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    • 2014
  • Drug delivery in human upper airway was studied by the numerical simulation of oral airflow. We created an anatomically accurate upper airway model from CT scan data by using a medical image processing software (Mimics). The upper airway was composed of oral cavity, pharynx, larynx, trachea, and second generations of branches. Thin sliced CT data and meticulous refinement of model surface under the ENT doctor's advice provided more sophisticated nasal cavity models. With this 3D upper airway models, numerical simulation was conducted by ANSYS/FLUENT. The steady inspiratory airflows in that model was solved numerically for the case of flow rate of 250 mL/s with drug-laden spray(Q= 20, 40, 60 mL/s). Optimal parameters for mechanical drug aerosol targeting of predetermined areas was to be computed, for a given representative upper airways. From numerical flow visualization results, as flow-rate of drug-laden spray increases, the drag spray residue in oral cavity was increased and the distribution of drug spray in trachea and branches became more homogeneous.

A Comparative Analysis of Elderly Intoxication Patient between Urban and Rural Area for the Safety Management and Emergency Care (농촌과 도시지역 노인약물중독환자의 응급처치와 약물중독안전관리에 대한 연구)

  • Rhim, Jae-Dong;Cho, Byung-Jun;Seoung, Youl-Hun;Kim, Seon-Rye
    • Journal of the Korea Safety Management & Science
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    • v.12 no.1
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    • pp.19-25
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    • 2010
  • To investigate acute drug intoxication trends in the elderly visited Emergency Medical Centers, Data was collected from the records of poisoning patients visited Five different Hospitals from January 1. 2007 to December 31. 2007. The analysis was conducted by using 135 cases of 624 cases. When considering only the elderly and making comparisons between the urban areas and the rural areas the following data was produced. In regard to patients with acute drug intoxication, the main substance of choice was pesticides. Cases of acute drug intoxication are definitely higher for those categorized as the rural elderly (75.0%) when compared with those categorized as the urban elderly (44.1%). The male to female ratio, those living together as a family, past suicide attempts, mental state and sobriety condition when they came, monthly distribution etc. between the two groups did not demonstrate a difference between them. In regard to reasons given for acute drug intoxication, suicide was the highest at 60.7% of the cases. When comparing accidental reasons for poisoning, the urban elderly, at 34.2% of their cases, were higher than in the rural elderly, at 23.7%. After first aid was administered, the admission rate was higher for the rural elderly (47.4%) than for the urban elderly (33.9%). This shows that the rural elderly have a more severe acute drug intoxication poisoning problem than the urban elderly do.

Self-organized Pullulan/Deoxycholic Acid Nanogels: Physicochemical Characterization and Anti-cancer Drug-releasing Behavior

  • Na, Kun;Park, Kyong-Mi;Jo, Eun-Ae;Lee, Kwan-Shik
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.11 no.3
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    • pp.262-267
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    • 2006
  • The objective of this study was to develop new self-organized nanogels as a means of drug delivery in patients with cancer. Pullulan (PUL) and deoxycholic acid (DOCA) were conjugated through an ester linkage between the hydroxyl group in PUL and the carboxyl group in DOCA. Three types of PUL/DOCA conjugates were obtained, differing in the number of DOCA substitutions (DS; 5, 8, or 11) per 100 PUL anhydroglucose units. The physicochemical properties of the resulting nanogels were characterized by dynamic light scattering, transmission electron microscopy, and fluorescence spectroscopy. The mean diameter of DS 11 was the smallest (approx. 100 nm), and the size distribution was unimodal. To determine the organizing behavior of these conjugates, we calculated their critical aggregation concentrations (CACs) in a 0.01-M phosphate buffered saline solution. They were $10.5{\times}10^{-4}mg/mL,\;7.2{\times}10^{-4} mg/mL,\;and\;5.6{\times}10^{-4} mg/mL$ for DS 5, 8, and 11, respectively. This indicates that DOCA can serve as a hydrophobic moiety to create self-organized nanogels. To monitor the drug-releasing behavior of these nanogels, we loaded doxorubicin (DOX) onto the conjugates. The DOX-loading efficiency increased with the degree of DOCA substitution. The release rates of DOX from PUL/DOCA nanogels varied inversely with the DS. We concluded that the PUL/DOCA nanogel has some potential for use as an anticancer drug carrier because of its low CAC and satisfactory drug-loading capacity.

Percutaneous Absorption Characteristics of Tacrine in Alzheimer-type Dementia Treatment (Alzheimer형 치매치료제인 Tacrine의 경피 투과 특성 연구)

  • Lee, Han-Seob
    • Journal of the Korean Applied Science and Technology
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    • v.29 no.4
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    • pp.552-560
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    • 2012
  • Drug delivery technologies are patent protected formulation technologies that modify drug release profile, absorption, distribution, and elimination for the benefit of improving product efficacy and safety, as well as patient convenience and compliance. The most commonly used transdermal system is the skin patch using various types of technologies. Compared with other method of dosage, it is possible to use for a long term. It is also possible to stop the drug dosage are stop if the drug dosage lead to side effect. Polysaccharide, such as karaya gum and locust bean gum(LBG)/water-soluble chitosan oligomer(WSCO) were selected as base materials of TDS. Also, these polymers were characterized in terms of enhancers, tacrine contents. Among these polysaccharide, the permeation rate of karaya gum matrix was fastest in tacrine such as lipophilic drug in vitro. We used glycerin, PEG 400, and PEG 800 as enhancers. Therefore, transdermal absorption of tacrine could be improved by changing vehicle composition or by using penetration enhancers. Especially it would be anticipated that the high permeation efficacy could be obtained by using vehicle that has enhancing effect for itself and by adding enhancers to it.

Effects of Hydrophilic Additives on the Release Rate of Protein Drugs (단백질 약물 방출속도에 미치는 친수성 첨가제의 영향)

  • Kwon, Young-Kwan;Kim, Ji-Hyeon;Yoo, Young-Je
    • KSBB Journal
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    • v.22 no.4
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    • pp.213-217
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    • 2007
  • It has been reported that hydrophobic additives generally decrease the release rate of protein drugs from drug delivery systems (DDS) and hydrophilic additives increase the release rate. In many cases, however, the addition of hydrophilic molecule is necessary for improving the stability of protein drugs. In the present work, the effects of hydrophilic additives on the release profiles, and micelle formation of protein drug formulations were investigated to develop a novel method for protein drug delivery. For model protein drug, bovine serum albumin (BSA) was employed and several hydrophilic additives were used in the release experiments. Hydrophilic additive D-sorbitol showed the lower release rates of BSA than other hydrophobic additives due to the gel strengthening ability of the additive and the optimum concentration of D-sorbitol was 3 w/v % for the retarded release rate. In addition, it was found that the addition of D-sorbitol was very effective for obtaining homogeneous and stable DDS. The results were discussed in terms of the micelle formation and the micelle structure, i.e., the differences in gel structure and the distribution of drugs in micelles.