• The Korean Journal of Physiology and Pharmacology
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• v.5 no.2
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• pp.107-122
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• 2001

A function of the kidney is elimination of a variety of xenobiotics ingested and wasted endogenous compounds from the body. Organic anion and cation transport systems play important roles to protect the body from harmful substances. The renal proximal tubule is the primary site of carrier-mediated transport from blood into urine. During the last decade, molecular cloning has identified several families of multispecific organic anion and cation transporters, such as organic anion transporter (OAT), organic cation transporter (OCT), and organic anion-transporting polypeptide (oatp). Additional findings also suggested ATP-dependent organic ion transporters such as MDR1/P-glycoprotein and the multidrug resistance-associated protein (MRP) as efflux pump. The substrate specificity of these transporters is multispecific. These transporters also play an important role as drug transporters. Studies on their functional properties and localization provide information in renal handling of drugs. This review summarizes the latest knowledge on molecular properties and pharmacological significance of renal organic ion transporters.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.193-194
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• 1998

Recently, evaluation of brain transport of taurine which is possible to effect on Alzheimer's disease has investigated in rats. Also, internal carotid artery perfusion (ICAP) method is very useful for measuring of blood-brain barrier (BBB) permeability in rats. But ICAP has difficulties to evaluate of BBB permeability in mice especially. In the present study examines neuropharmaceutials permeability through the BBB in mice by common carotid artery perfusion (CCAP) method that modify ICAP method and require simple surgery. The external carotid artery (ECA) is cannulated with coagulating pterygopalatine artery (PPA) on ICAP method, while CCA is cannulated without coagulating PPA on CCAP method. The CCAP method require 4-5 fold higher infusion rate than ICAP method because an additional factor of 2 must be incorporated to adjust for fluid loss to the extracerebral circulation.

• Journal of Pharmaceutical Investigation
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• v.38 no.4
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• pp.255-259
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• 2008

The present study aimed to investigate the in-vitro characteristics of N4-amino acid derivatives of cytarabine for the oral delivery of cytarabine. After the synthesis of L-Ile-cytarabine, L-Leu-cytarabine and L-Arg-cytarabine, the gastrointestinal stability of each prodrug was examined using artificial gastric juice and intestinal fluids. The cellular uptake characteristics of prodrugs were also examined in Caco-2 cells. While L-Ile-cytarabine and L-Leu-cytarabine appeared to be stable in all the tested biological media during 4-hr incubation, L-Arg-cytarabine was rapidly disappeared within 5 min. Accordingly, the cellular uptake of L-Ile-cytarabine and L-Leu-cytarabine was significantly higher than that of its parent drug, cytarabine in Caco-2 cells but the cellular uptake of L-Arg-cytarabine was similar to that from its parent drug. The cellular uptake of L-Ile-cytarabine and L-Leu-cytarabine appeared to be saturable as drug concentration increased from 0.4 to 4 mM. Collectively, L-Ile-cytarabine and L-Leu-cytarabine could be promising candidates to improve the oral absorption of cytarabine via a saturable transport pathway.

• Membrane Journal
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• v.18 no.2
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• pp.124-131
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• 2008

The biodegradable hyaluronic acid membranes cross-linked with lactide using the crosslinking agent, 1,3-butadiene diepoxide (BD), were prepared as a potential biocompatible material for tissue engineering. The degree of lactide and BD reaction of the crosslinked membrane was determined by the analysis of nuclear magnetic resonance spectroscopy 6% of growth inhibition was observed in case of high BD concentration but the value is low enough not to affect cell growth. As the crosslinking reaction temperature increased, elongation increased and swelling ratio decreased. The rate of degradation was found to increase with the crosslinking temperature. The drug release experiment showed that the transport of drug through the membrane decreased with the crosslinking temperature.

• Microbiology and Biotechnology Letters
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• v.31 no.3
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• pp.230-234
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• 2003

The Bacillus subtilis YvaE protein, the small multidrug resistance (SMR) family (TC #2.A. 7.1), is shown to catalyze efflux of multiple cationic drugs including many disinfectants, when it was cloned and expressed in Escherichia coli. When the yvaD gene was coexpressed with yvaE gene, the yvaD protein, encoded within a single operon with the yvaE gene, is shown to counteract the action ofYvaE. By ethidium efflux analysis, the cells harvoring a vector with yvaE gene showed a rapid ethidium efflux, compared with the control cells. These results clearly suggest that YvaE mediates drug export from the cell cytoplasm.

• Translational and Clinical Pharmacology
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• v.26 no.3
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• pp.103-110
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• 2018

The human microbiome is known to play an essential role in influencing host health. Extracellular vesicles (EVs) have also been reported to act on a variety of signaling pathways, distally transport cellular components such as proteins, lipids, and nucleic acid, and have immunomodulatory effects. Here we shall review the current understanding of the intersectionality of the human microbiome and EVs in the emerging field of microbiota-derived EVs and their pharmacological potential. Microbes secrete several classes of EVs: outer membrane vesicles (OMVs), membrane vesicles (MVs), and apoptotic bodies. EV biogenesis is unique to each cell and regulated by sophisticated signaling pathways. EVs are primarily composed of lipids, proteins, nucleic acids, and recent evidence suggests they may also carry metabolites. These components interact with host cells and control various cellular processes by transferring their constituents. The pharmacological potential of microbiome-derived EVs as vaccine candidates, biomarkers, and a smart drug delivery system is a promising area of future research. Therefore, it is necessary to elucidate in detail the mechanisms of microbiome-derived EV action in host health in a multi-disciplinary manner.

• 대한핵의학회:학술대회논문집
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• 2001.05a
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• pp.66-75
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• 2001

Although diverse mechanisms are involved in multidrug resistance for chemotherapeutic drugs, the development of cellular P-glycoprotein(Pgp) and multidrug-resistance associated protein (MRP) are important factors in the chemotherapy failure to cancer. Various detection assays provide information about the presence of drug efflux pumps at the mRNA and protein levels. However these methods do not yield information about dynamic function of Pgp and MRP un vivo. Single photon emission tomography (SPECT) and positron emission tomography (PET) are available for the detection of Pgp and MRP-mediated transport. $^{99m}Tc$-sestaMIBl and other $^{99m}Tc$-radiopharmaceuticals are substrates for Pgp and MRP, and have been used in clinical studies for tumor imaging, and to visualize blockade of Pgp-mediated transport after modulation of Pgp pump. Colchicine, verapamil and daunorubicin labeled with $^{11}C$ have been evaluated for the quantification of Pgp-mediated transport with PET in vivo and reported to be feasible substrates with which to image Pgp function in tumors. Leukotrienes are specific substrates for MRP and N-$[^{11}C]$acetyl-leukotriene E4 provides an opportunity to study MRP function non-invasively in vivo. Results obtained from recent publications are reviewed to confirm the feasibility of using SPECT and PET to study the functionality of MDR transporters in vivo.

• Journal of Pharmaceutical Investigation
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• v.38 no.3
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• pp.183-189
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• 2008

The present study compared the feasibility of Caco-2 and MDCK cells as an efficient in-vitro model for the drug classification based on Biopharmaceutics Classification System (BCS) as well as an in-vitro model for drug interactions mediated by P-gp inhibition or P-gp induction. Thirteen model drugs were selected to cover BCS Class I{\sim}IV$ and their membrane permeability values were evaluated in both Caco-2 and MDCK cells. P-gp inhibition studies were conducted by using vinblastine and verapamil in MDCK cells. P-gp induction studies were also performed in MDCK cells using rifampin and the P-gp expression level was determined by western blot analysis. Compared to Caco-2 cells, MDCK cells required shorter period of time to culture cells before running the transport study. Both Caco-2 and MDCK cells exhibited the same rank order relationship between in-vitro permeability values and human permeability values of all tested model compounds, implying that those in-vitro models may be useful in the prediction of human permeability (rank order) of new chemical entities at the early drug discovery stage. However, in the case of BCS drug classification, Caco-2 cells appeared to be more suitable than MDCK cells. P-gp induction by rifampin was negligible in MDCK-cells while MDCK cells appeared to be feasible for P-gp inhibition studies. Taken all together, the present study suggests that Caco-2 cells might be more applicable to the BCS drug classification than MDCK-cells, although MDCK cells may provide some advantage in terms of capacity and speed in early ADME screening process.

• Korean Chemical Engineering Research
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• v.43 no.2
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• pp.299-304
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• 2005

There have been many efforts to use anionic hydrogels as oral protein delivery carriers due to their pH-responsive swelling behavior. The dynamic swelling behavior of poly(methacrylic acid-co-methacryloxyethyl glucoside) [P(MAA-co-MEG)] hydrogels was investigated to determine the mechanism of water transport through these anionic hydrogels. The exponential relation $M_t/M_{\infty}=kt^n$ was used to calculate the exponent, n, describing the Fickian or non-Fickian behavior of swelling polymer networks. The mechanism of water transport through these gels was significantly affected by the pH of the swelling medium. The mechanism of water transport became more relaxation-controlled in the swelling medium of pH 7.0 that was higher than the $pK_a$ of the gels. Experimental results of time-dependent swelling behavior of the gels were analyzed with several mathematical models. Using ATR-FTIR spectroscopy, the effect of ionization of the carboxylic acid groups in the polymer networks on the water transport mechanism was investigated.

• Archives of Pharmacal Research
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• v.10 no.4
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• pp.250-257
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• 1987

The development of physiologically based pharmacokinetic model for drug distribution and excretion is described. The physiological modeling procedure is useful in animal and clinical applications to obtain fundamental knowledge of the transport and metabolism of a substance in vivo. In this paper a review of physiologically based pharmacokinetics is presented in the hope of understanding and increasing the use of this modelling technique. The method of model development and the composition of equations based on the different models are explained. For the better understanding a physiological pharmacokinetic model of tenoxicam disposition in the rat is presented as an example of flow limited model.