• Bulletin of the Korean Chemical Society
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• v.29 no.1
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• pp.51-56
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• 2008

The regioselective ring opening of epoxides using elemental iodine and bromine in the presence of methimazole (MMI, a anti-thyroid drug) and its metabolite methimazole-disulfide as new catalysts are studied. MMI easily converted in vitro to MMI-disulfide without any double activation presented in vivo. FT-Raman and UV spectroscopies are used to study the interaction of iodine with these catalysts. The results indicate that both catalysts are efficient in polyiodide formation, but MMI-disulfide can catalyze this reaction in higher yield and regioselectivity. The complex [(MMI-disulfide)I]+.I3- is considered to be formed initially which could be bulkier by addition of excess of iodine in the course of the reaction. These bulky nucleophiles have a fundamental role in the high regioselectivity by attacking the less sterically hindered epoxide carbon. In this study we suggest that MMI is readily converted to MMI-disulfide by interaction with iodine or activated iodine in thyroid gland, and this process is responsible for high anti-thyroid activity of MMI.

• YAKHAK HOEJI
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• v.49 no.5
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• pp.380-385
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• 2005

The aim of this study is to investigate the effects of verapamil on the pharmacokinetics of tamoxifen following oral administration of tamoxifen with verapamil to rats. Tamoxifen (10 mg/kg) was administered orally in the presence or absence of verapamil (1, 3 or 6 mg/kg). Compared to the control group (given tamoxifen alone), the presence of verapamil significantly (p<0.05 by 1 mg/kg, p<0.01 by 3 and 6 mg/kg) increased the areas under the plasma concentration-time curve (AUC) and the peak concentrations ($C_{max}$) of tamoxifen. Consequently, the relative bioavailability ($RB\%$) of tamoxifen with verapamil was 1.6-2.1 fold higher than that of the control. But the time to reach peak concentration ($T_{max}$) and the terminal half-life ($t_{1/2}$) of tamoxifen were not altered significantly in the presence of verapamil. The increased AUC and $C_{max}$ of tamox­ifen in the presence of verapamil might be associated with the inhibition by verapamil of the P-glycoprotein and the first­pass metabolizing enzyme CYP3A4 in small intestinal mucosa. The drug interaction should be taken into consideration when tamoxifen is used to the patient with verapamil in the clinical setting.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.97-97
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• 1995

On the combination of antacid, the pharmacokinetics and gastric adhesion of $\^$14/C-aceglutamide aluminum complex($\^$14/C-AGA) were examined in rats. Specially, This study was focused on the drug interaction that the coadministration of antacid may affect the oral absorption and gastric adhesion of aceglutamide aluminum complex(AGA). After the oral administration of $\^$14/C-AGA and antacid to rats, the radioactivity of plasma and urinary recovery was lower than that of $\^$14/C-AGA administered group. Relatively, the cumulative recovery of radioactivity in feces was increased significantly. The comparative bioavailability of $\^$14/C-AGA from the plasma concentration-time curve and urinary recovery was about 60%. in vitro, the effect of antacid in the gastric adhesion of AGA was not significantly different between AGA and AGA/antacid treatment. And it accorded well with the result of in vivo experiment. In conclusion, on the combination of antacid, the oral absorption of AGA was decreased but the gastric adhesion was not affected in respect of drug interaction.

• YAKHAK HOEJI
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• v.39 no.6
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• pp.577-584
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• 1995

On the combination of antacid, the pharmacokinetics and gastric adhesion of [$^{14}c$]aceglutamide aluminium complex([$^{14}C$]AGA) were examined in rats. Specially, this study was focused on the drug interaction that the co-administration of antacid may affect the oral absorption and gastric adhesion of aceglutamide aluminium complex(AGA). In the study of the oral co-administration of [$^{14}C$] AGA and antacid(aluminium hydroxide and magnesium hydroxide(AM)), the radioactivity of plasma and urinary recovery was lower than that of [$^{14}C$]AGA alone administered group. However, the cumulative recovery of radioactivity in feces was increased significantly. The comparative bioavailability of [$^{14}C$] AGA from the plasma concentration-time curve and urinary recovery was about 60%. In vitro, the effect of antacid on the gastric adhesion of AGA was not significatly different between AGA and AGA/antacid treatment. And it accorded well with the result of in vivo experiment. In conclusion, on the combination of antacid, the oral absorption of AGA was decreased by the gastric adhesion was not affected in respect of drug interaction.

• YAKHAK HOEJI
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• v.47 no.2
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• pp.98-103
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• 2003

The purpose of this study was to investigate the effect of flavone (20 mg/kg) on the pharmacokinetic parameters and the bioavailability of paclitaxel (40 mg/kg) orally coadministered in rats. The plasma concentration of paclitaxel in combination with flavone was increased significantly (coadministration p＜0.05, pretreatment p＜0.0l) compared to that of control. Area under the plasma concentration-time curve (AVC) of paclitaxel with flavone was significantly (coadministration p＜0.05, pretreatment p＜0.0l) higher than that of control. Peak concentration (Cmax) of paclitaxel with flavone were significantly increased (coadministration p＜0.05, pretreatment p＜0.01) compared to that of control. Time to peak concentration (Tmax) of paclitaxel with flavone decreased significantly (p＜0.05) than that of control. The total body clearance (CLt) and elimination rate constant ($\beta$) of paclitaxel with flavone were significantly reduced (p＜0.05) compared to those of control. Half-life (t$_{1}$2/) of paclitaxel with flavone was significantly prolonged (p＜0.05) compared to that of control. Based on these results, it might be concluded that flavone may enhance bioavailability of paclitaxel through the inhibition of cytochrome P450 and P-glycoprotein, which are engaged in paclitaxel absorption and metabolism in liver and gastrogintestinal mucosa, respectively.

• Analytical Science and Technology
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• v.35 no.2
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• pp.60-68
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• 2022

In this study, we developed and validated a sensitive analytical method to quantify baphicacanthin A in mouse plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The standard calibration curves for baphicacanthin A ranged from 0.5 to 200 ng/mL and were linear, with an r² of 0.985. The inter- and intra-day accuracy and precision and the stability fell within the acceptance criteria. Besides, we investigated the pharmacokinetics of baphicacanthin A following its intravenous (5 mg/kg) and oral administration (30 mg/kg). Intravenously injected baphicacanthin A showed biphasic elimination kinetics with high clearance and volume of distribution values. Furthermore, baphicacanthin A showed a rapid absorption but low aqueous solubility (182.51±0.20 mg/mL), resulting in low plasma concentrations and low oral bioavailability (2.49 %). Thus, we successfully documented the pharmacokinetic properties of baphicacanthin A using this newly developed sensitive LC-MS/MS quantification method, which could be used in future lead optimization and biopharmaceutic studies.

• Journal of Pharmaceutical Investigation
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• v.41 no.1
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• pp.45-50
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• 2011

Nonclassical pathway of crystallization has been utilized to modify the properties and morphologies of inorganic and organic/inorganic materials. In here, the polymer-directed crystallization method has been applied to the pharmaceutical active ingredient to assess the applicability for as a particle engineering tool. The polymer-directed crystallization was successful to modifying the crystal size, habit and morphology, but it was not effective to discover the novel polymorphs of Sibutramine (SB). SB was selected as a model drug and polyacrylic acid (PAA), polyethylene imine (PEI) and chitosan (CHI) were added as a crystallization pathway modifier. SB was crystallized via drowning crystallization using methanol or ethanol as a solvent and water as a non-solvent. The significant interactions between polymer and the drug were confirmed by measuring the solubility of the drug in presence of polymer during the crystallization. The crystal forms of SB are characterized by X-ray diffraction (XRD), scanning electron microscope (SEM) and optical microscope (OM). The polymer-directed crystallization seems to be able to modify the crystal properties of pharmaceutical active ingredient, which is critical in determining the bioavailability, processability, and stability.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2008.04a
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• pp.89-99
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• 2008

GPCRs are large families of cell surface receptors that transmit signals through conformational changes upon ligand activation and an interaction with the heterotrimeric G-proteins. GPCRs regulate the cell-signaling pathways and participate in the regulation of physiological processes through the G-proteins defined by their ${\alpha}$ subunits. A family of 20 G protein-coupled receptors (GPCRs) that provide a large class of tractable drug targets for new anti-inflammatory drugs and, in certain instances, for the treatment of the inflammatory indications such as atherosclerosis, rhinitis, asthma, pulmonary disease and arthritis. In view of the important findings showing that $G{\alpha}_{12}/G{\alpha}_{13}$ regulate the various cellular processes such as actin-stress fiber formation, neurite retraction, platelet aggregation, gene induction, and apoptosis, we became interested in whether, after coupling to the activated GPCRs, the G-proteins and their downstream molecules might be involved in the pathologic processes of chronic inflammatory diseases (e.g., liver fibrosis). In this symposium, the possible link of the G-proteins with the pathophysiology will be discussed with the aim of finding potential new drug targets.

• Proceedings of the Korean Vacuum Society Conference
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• 2016.02a
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• pp.105.2-105.2
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• 2016

For the rational design and facile fabrication of novel nanostructures, we present a new approach to generating arrays of three-dimensionally tunable nanostructures by exploiting light-matter interaction. To create controlled three-dimensional (3D) nanostructures, we utilize the 3D spatial distribution of light, induced by the light-matter interaction, within the matter to be patterned. As a systematic approach, we establish 3D modeling that integrates the physical and chemical effects of the photolithographic process. Based on a comprehensive analysis of structural formation process and nanoscale features through this modeling, we are able to realize three-dimensionally tunable nanostructures using facile photolithographic process. Here we first demonstrate the arrays of three-dimensionally controlled, stacked nanostructures with nanoscale, tunable layers. We expect that the promising strategy would open new opportunities to produce the arrays of tunable 3D nanostructures using more accessible and facile fabrication process for various biomedical applications ranging from biosensors to drug delivery devices.

• Journal of Pharmaceutical Investigation
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• v.27 no.1
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• pp.51-56
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• 1997

This study was attempted to investigate the pharmacokinetic interaction of vancomycin (10 mg/kg, i.v.) and probenecid (7.5. 15, and 30 mg/kg, oral) in rabbits. The area under curve (AUC) of plasma vancomycin concentration was significantly increased (p<0.01) in rabbits when the probenecid was coadministrated. Volume of distribution (Vd) was significantly decreased (p<0.05) in rabbits coadministrated with probenecid (15 and 30 mg/kg) and total body clearance (CLt) was decreased significantly (p<0.05. p<0.01) in rabbits coadministrated with probenecid (7.5, 15 and 30 mg/kg). There was significant correlation between AUC and probenecid dose. From the results of this experiment, it is desirable to adjust dosage regimen of vancomycin for reduction of side or toxic effect when the probenecid is coadministered in clinical practice.