• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.10a
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• pp.135-136
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• 1995

Resent advances in computer technology have introduced a sophisticated capability for computing the biological fate of toxicants in a biological system. This methodology, which has drastically altered risk assessment skill in toxicology, is designed using all the mechanistic information, and all claim better accuracy with extrapolating capability Iron animal to people than conventional pharmacokinetic methods. Biologically based mathematical models in which the specific mechanistic steps governing tissue disposition(pharmacokinetics) and toxic action (pharmacodynamics) of chemicals are constructed in quantitative terms by a set of equations loading to prediction of the outcome of specific toxicological experiments by computer simulation. pharmacokinetic and pharmacodynamic models are useful in risk assessment because their mechanistic biological basis permits the high-to-low dose, route to route and interspecies extrapolation of the tissue disposition and toxic action of chemicals.

• Journal of Biomedical Engineering Research
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• v.9 no.1
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• pp.73-78
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• 1988

The polymer electrolyte complex hydrogels consisting of poly (methacrylic acid) and poly (4-vinylpyrridine) were formed and 5-flurouracil and pilocarpine drugs were loaded on their hydrogels. Cumulative 5-FU released from PEC hydrogel was affected by the degree of loading and release rate of 5-FU was followed by the monolithic type. Cumulative pilocarpine released from PEC hydrogel increased by ionic interaction between cationic pilocarpine and anionic PMA. Release rate showed the zero order after burst effect.

• Proceeding of EDISON Challenge
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• 2015.03a
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• pp.212-216
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• 2015

Oseltamivir, also known as Tamifu, is an inhibitor of neuraminidase protein which plays an essential role in proliferation and replication of influenza virus. Binding to the active site of neuraminidase, the oseltamivir prevents the protein from enzyme reaction. Conformational change of the protein(neuraminidase) should be accompanied by the enzyme reaction, but the drug inhibits the protein to deform. In this study, we examine the influence of oseltamivir on protein's conformational change in the structural and mechanical point of view. Finite element analysis of the protein can be an useful approach to investigate the influence of oseltamivir on the deformation of a protein. We suggest the finite element based protein model, and then perform the linear static analysis with the displacement loading condition based on the first two largest motion which can be obtained from the normal mode analysis. The results show that it takes more energy to change shape of the protein with an oseltamivir attached than the protein without an oseltamivir.

• Journal of the Korean Chemical Society
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• v.47 no.5
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• pp.479-486
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• 2003

In this study, poly(DL-lactide-co-glycolide) nanoparticles loaded with water-insoluble vitamins such as vitamin A (Retinol) and vitamin E acetate were prepared by the emulsification diffusion method. Polymer solution was prepared by the two water-miscible organic solvent, such as ethanol and acetone. Because of its biocompatible property, polyethyleneglycol-polypropyleneglycol diblock copolymer was used as surfactant and stabilizer. The influence of some preparative variables on the nanoparticle formation and on the loading efficiency of active agents, such as the type and concentration of stabilizing agent, the stirring methods, the water/oil phase ratio and the polymer concentration were investigated in order to control and optimize the process. After preparation of nanoparticles loaded with active agent, particle size and distribution were evaluated by the light scattering particle analyzer. The loading efficiency of active agents was evaluated by the UV-visible spectroscopy. As the results, particle size were 50-200 nm and dispersibility was monodisperse. The optimum loading efficiency of active agents was observed 50-60%. It was found that the appropriate of selections of binary solvent mixtures and polymeric concentrations in both organic and aqueous phases could provide good yield and favorable physical properties of PLGA nanoparticles.

• Korean Journal of Clinical Pharmacy
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• v.15 no.2
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• pp.105-117
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• 2005

Following intracoronary stenting, antiplatelet therapy lead to greater protection from thrombotic complication. A few data are available about the effect of clopidogrel versus cilostazol, an antiplatelet commonly used after intracoronary stenting. To evaluate the efficacy and safety of clopidogrel plus aspirin compared with those of cilostazol plus aspirin in coronary stenting and to evaluate the efficacy of clopidogrel loading dose prior to coronary stealing in clopidogrel group. Data were retrospectively collected from medical charts of patients who had undergone coronary stenting and received either clopidogrel with or without loading 300 mg followed by 75 mg/d (n=58), or 200 mg/d cilostazol(n=72) for 1 year, between January 2000 and May 2002. All patients in both groups received aspirin 200 mg/d throughout the study. The primary endpoints at 7, 30, 180 and 365 days after stealing were the composite of death, Myocardial Infarction, stroke, angina, and revascularization in the intent to treat population and restenosis at follow up angiography. The secondary endpoints were the incidence of bleeding complications at 7, 30, and 365 days, and durg adverse effects at 365 days after stenting. At 180 and 365 days after stenting, the combined primary endpoints were significantly reduced in clopidogrel plus aspirin group (relative risk 0.39; 95% CI 0.17 to 0.92; p=0.021, RR 0.43; 95% CI 0.22 to 0.84; p=0.0085, respectively). However, the combined primary endpoints were not significantly different between the two groups at 7 and 30 days (p:1.00, p=0.79, respectively). Angiographic restenosis rate was 14.3% in clopidogrel plus aspirin uoup and 32.1% in cilostazol plus aspirin group (p=0.19). 300mg of clopidogrel loading dose did not significantly reduce the combined primary endpoints at 30 days after stenting (RR 0.14; 95% CI 0.01 to 2.65; p=0.23). The rate of bleeding complications and drug adverse effects were not different between the two groups. In patients undergoing intracoronary stenting, clopidogrel plus aspirin therapy is more beneficial than cilostazol plus aspirin in reducing major adverse cardiac events with similar rate of bleeding complication. A loading dose of clopidogrel did not lead to a statistically significant reduction in major adverse cardiac events.

• Journal of Pharmaceutical Investigation
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• v.33 no.4
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• pp.319-322
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• 2003

Many studies have been attempted to overcome the problems of paclitaxel related to the extremely low aqueous solubility of paclitaxel and the unexpected side-effects caused by $Cremophor^{\circledR}$ EL in a commercial paclitaxel formulation, $Taxol^{\circledR}$. In order to formulate a new delivery system suitable for intravenous administration without toxic excipients, in this study, paclitaxel was incorporated into solid lipid nanoparticles (Px-SLN) by hot homogenization technique using a microfluidizer. Particle size and zeta potential were measured by a Zetasizer. In vitro drug release experiment was performed by a dialysis diffusion method. Each Px-SLN or $Taxol^{\circledR}$ was intravenously administered to the male Sprague-Dawley rats at a dose of 5 mg/kg as paclitaxel. Blood samples were deproteinated with acetonitrile and assayed for paclitaxel by the validated HPLC/MS/MS method. Mean particle size and zeta potential were measured as 72.1 nm (< Polydispersity 0.3) and -41.5 mV, respectively. The content of paclitaxel in SLN was 1.42 mg/ml and the drug loading efficiency was $71.2{\pm}4.3%$. The $AUC_t$ of Px-SLN was 3.4-fold greater than that of $Taxol^{\circledR}$. The Px-SLN might be a promising candidate for an alternative formulation for the parenteral delivery of paclitaxel.

• The Korean Journal of Pain
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• v.12 no.2
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• pp.200-204
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• 1999

Background: Patient-controlled analgesia (PCA) has proven to be safe and effective in children from age 5 years, and older and compares favourably with continuous morphine infusion in the older child. We compared fentanyl and butorphanol for opioid use in PCA with ketorolac to determine a suitable drug combination for post-tonsillectomy pain control. Methods: We studied 60 patients, aged 5~12 yrs, undergoing tonsillectomy with or without adenoidectomy under general anesthesia using $N_2O-O_2$-enflurane. Patients were randomly assigned to receive fentanyl $250\;{\mu}g$ (Group 1: n=30) or butorphanol 5 mg (Group 2: n=30) mixed with ketorolac 90 mg and ondansetron 4 mg diluting 100 ml of 5% D/W solutions intravenously via PCA pump after operation. PCA pump were programmed to deliver a 0.05 ml/kg loading dose, 0.01 ml/kg/hr basal infusion, 0.01 ml/kg on demand bolus, 6 min lockout intervals between doses and 4 bolus hourly limit. Total infusion dosage of PCA drug, VAS pain scores, side effects and satisfaction score of both groups were monitored for 48 hrs. Results: Total infusion dosages were fentanyl $170.6\;{\mu}g$ with ketorolac 61.4 mg (Group 1) and butorphanol 2.8 mg with ketorolac 50.4 mg (Group 2). Total infusion dosage, quality of analgesia, side effects and overall satisfaction didn't differ between two groups. Conclusions: Both fentanyl and butorphanol mixed with ketorolac were effective for post-tonsillectomy pain control using PCA pump in children as young as 5 years old.

• Journal of Pharmaceutical Investigation
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• v.36 no.2
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• pp.97-102
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• 2006

The aim of this study was to investigate the feasibility and optimize permeability of slim patch type as a transdermal delivery system of caffein. Slim patch type was formulated and tested in modified Franz diffusion cell across cellulose membrane and hairless mouse skin in pH 5.8 phosphate buffer solution (PBS). The effect of $Pharmsolv^{\circledR}$ and drug concentration on permeation at four model, 1,2% $Pharmsolv^{\circledR}$ with $0.12\;mg/cm^2$ caffein and 0.12, $1.2\;mg/cm^2$ caffein with 2% $Pharmsolv^{\circledR}$ through hairless mouse skin was studied in vitro. The release of caffein from slim patch with various loading was fitted by the Higuchi's diffusion equation. The result showed that chemical $Pharmsolv^{\circledR}$ produced a large and significant increase of permeation. The effect of 2% $Pharmsolv^{\circledR}$ on permeation of caffein was greater about 10-fold greater than 1% $Pharmsolv^{\circledR}$ in first 60 minutes. The effect of drug concentration, however, was lower than that produced by chemical $Pharmsolv^{\circledR}$. Within the tested system, the most efficient combination for caffein slim patch type was $0.12\;mg/cm^2$ caffein with 2% $Pharmsolv^{\circledR},$ although $1.2\;mg/cm^2$ caffein with 2% $Pharmsolv^{\circledR}$ showed highest amounts permeation, because permeated percentages were significantly lower about $1/4{\sim}1/5$ times.

• Journal of Pharmaceutical Investigation
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• v.39 no.6
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• pp.423-429
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• 2009

Liposomes have been used as one of the efficient carriers for drug delivery. In this study, anionic liposomes of which surface was modified by using both electrostaic interaction between anionic liposomes and cationically charged BSA molecules at lower pH than isoelectric point (pI) of BSA and denaturation of the BSA-coated liposomes by thermal treatment. The thermally denatured BSA-coated liposomes (DBAL) had mean particle diameter of 125.2${\pm}$1.7 nm and zeta potential value of -22.4${\pm}$4.5 mV. Loading efficiency of model drug, doxorubicin (DOX), into liposomes was 83.0${\pm}$2.6%. Results of in vitro stability study of DBAL in blood plasma showed that the mean particle diameter of DBAL 400 did not increase in blood plasma and adsorption of plasma protein was much less than plain or anionic liposomes. Intracellular uptake of DBAL 400 evaluated by confocal microscopy observation was higher than that of PEG liposomes.

• Polymer(Korea)
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• v.25 no.6
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• pp.884-892
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• 2001

Biodegradable wafers were prepared with poly (L-lactide-co-glycolide) (50 : 50 mole ratio of lactide to glycolide, molecular weight:5000 g/mole) by direct compression method for the sustained release of nifedipine to investigate the possibility of the treatment of hypertension. PLGA wafers were prepared by altering initial drug/polymer loading ratio, wafer thickness, and hydroxypropyl methylcellulose (HPMC) content. These wafers showed new zero-order release patterns for 11 days, and various biphasic release patterns could be obtained by altering the composition of wafers such as addition of matrix binder as HPMC to the PLGA wafer to reduce release rate of initial phase. The onset of polymer mass loss only occured after 4 days and about 40% of mass loss was observed after 11 days nifedipine release. This system had advantages in terms of simplicity in design and obviousness of drug release rate and may be useful as an implantable dosage form.